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PubMed2024

Tear fluid reflects the altered protein expressions of Alzheimer's disease patients in proteins involved in protein repair and clearance system or the regulation of cytoskeleton.

BackgroundNew biomarkers that improve diagnosis of Alzheimer's disease (AD) are warranted. Tear fluid (TF) containing variety of proteins that reflect pathophysiological changes of systemic diseases makes TF proteins potential biomarker candidates for AD.ObjectiveWe investigated the expression levels of TF proteins in persons with mild AD and cognitively healthy controls (CO) to find out if altered proteins may link to the AD pathophysiology.MethodsWe analyzed the data of the 53 study participants (34 COs, mean age 71 and Mini-Mental State Examination (MMSE) 28.9 ± 1.4 and 19 persons with AD, CDR 0.5-1, mean age 71 and MMSE 23.8 ± 2.8). All went through neurological status examination, cognitive tests, and ophthalmological examination. TF was collected using Schirmer strips. The TF protein content was evaluated via mass spectrometry-based proteomics and label-free quantification.ResultsEleven proteins having a role either in protein repair and clearance system, or regulation of cytoskeleton, showed altered expression in AD group compared to CO group. Seven of them were significantly (p ≤ 0.05) upregulated (Sti1, Twf1, Myl6, Otub1, Pls1 and Caza1) or, downregulated (HSP90) in AD group.ConclusionsAltered expression of all these up- or downregulated proteins may be linked to AD pathophysiology. Thus, our results are encouraging for searching new biomarker candidates for AD. TF is potential biomarker candidate, because TF seems to reflect altered protein levels already in mild AD dementia.

Humans↗

PubMed1977

Protein modification enzymes associated with the protein-synthesizing complex from rabbit reticulocytes. Protein kinase, phosphoprotein phosphatase, and acetyltransferase.

A number of protein modification activities are present in the protein-synthesizing complex isolated from rabbit reticulocytes. These enzymes are solubilized by sedimentation of the ribosomes through buffered sucrose containing 0.5 M KCl, and have been partially purified from the high salt wash fraction by chromatography on DEAE-cellulose and phosphocellulose. The ribosomal-associated enzymatic activities include cyclic AMP-regulated and cyclic nucloetide-independent protein kinase, phosphoprotein phosphatase, and acetyltransferase activities. These enzymatic activities have been shown to modify specific ribosomal and ribosomal-associated proteins. The cycli c AMP-regulated protein kinase phosphorylate the 40 S ribosomal subunit from rabbit reticulocytes. One of the cyclic nucleotide-independent protein kinase catalyzes the phosphorylation of two different factors involved in the initiation of hemoglobin synthesis. A single phosphoprotein phosphatase activity is shown to remove phosphate from 40 S ribosomal subunits. The major acetyltransferase activity associated with ribosomes acetylates a 60 S ribosomal protein.

Acetyl-CoA C-Acetyltransferase↗

PubMed2026

tRUBY: A convenient in planta tool for the detection of protein-DNA and protein-protein interactions.

Elucidating molecular interactions such as protein-DNA (PDIs) and protein-protein (PPIs) has traditionally relied on yeast-based 1-hybrid (1H) and 2-hybrid (2H) systems. To provide an alternative platform that better reflects the native cellular environment of plants, we optimized the tRUBY reporter system for 1H and 2H assays in Nicotiana benthamiana, enabling direct in planta analysis of PDIs and PPIs. Specifically, the 2A peptide sequence used for co-expressing the 3 betalain biosynthetic genes-responsible for the visible RUBY coloration-was replaced with T2A from the Thosea asigna virus in place of P2A or F2A from mammalian-pathogenic Picornaviridae viruses, improving biosafety for agricultural applications. The resulting tRUBY-1H and tRUBY-2H systems operate under near-physiological conditions with physiologically relevant expression levels, enabling quantitative, multiplexed, and directly compatible protein-level analyses, thereby offering high sensitivity and flexibility for advanced molecular studies. Ultimately, these systems demonstrate that the streamlined, cost-effective, and visually scorable in planta platform provided by RUBY is well-suited for intuitive, non-destructive monitoring of molecular interactions in plant tissues.

Nicotiana↗

PubMed1978

Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency.

Cobalamin (Cbl; vitamin B(12)) malabsorption in pancreatic insufficiency can be partially corrected by bicarbonate and completely corrected by pancreatic proteases but the mechanisms involved are unknown. Because saliva contains enough R-type Cbl-binding protein (R protein) to bind all of the dietary and biliary Cbl, it is possible that R protein acts as an inhibitor of Cbl absorption and that pancreatic proteases are required to alter R protein and prevent such inhibition. To test this hypothesis we studied the ability of R protein and intrinsic factor (IF) to compete for Cbl binding and ability of pancreatic proteases to alter this competition. Human salivary R protein bound Cbl with affinities that were 50- and 3-fold higher than those of human IF at pH 2 and 8, respectively. Cbl bound to IF was transferred to an equal amount of R protein with t((1/2))'s of 2 and 90 min at pH 2 and 8, respectively, and within several hours respective ratios of R protein-Cbl/IF-Cbl of 50 and 2 were observed. Cbl bound to R protein was not transferred to IF at either pH 2 or 8. Incubation of R protein with pancreatic proteases at pH 8 led to a 150-fold decrease in its affinity for Cbl. Incubation of R protein-Cbl with pancreatic proteases led to complete transfer of Cbl to IF within 10 min. Gel filtration studies with R protein-[(57)Co]Cbl and (125)I-R protein showed that pancreatic proteases partially degraded R protein. Pancreatic proteases differed in their ability to effect these changes with trypsin > chymotrypsin > elastase. Pancreatic proteases did not alter IF in any of the parameters mentioned above. Pepsin failed to alter either R protein or IF. THESE STUDIES SUGGEST THE FOLLOWING: (a) that Cbl is bound almost exclusively to R protein in the acid milieu of the stomach, rather than to IF as has been assumed previously; (b) that Cbl remains bound to R protein in the slightly alkaline environment of the intestine until pancreatic proteases partially degrade R protein and enable Cbl to become bound exclusively to IF; and (c) that the primary defect in Cbl absorption in pancreatic insufficiency is a lack of pancreatic proteases and a failure to alter R protein and effect the transfer of Cbl to IF. These studies also suggest that the partial correction of Cbl malabsorption observed with bicarbonate is due to neutralization of gastric HCl, since at slightly alkaline, pH IF can partially compete with R protein for the initial binding and retention of Cbl.

Carrier Proteins↗

PubMed1976

Protein kinases associated with peripheral nerve myelin. 1. Phosphorylation of endogenous myelin proteins and exogenous substrates.

When highly purified myelin from rat sciatic nerve was incubated with [gamma-32P]ATP, protein components of the membrane were phosphorylated indicating the presence of both the substrate (receptor protein) and an endogenous kinase in the membrane. Polyacrylamide gel electrophoresis of the phosphorylated membrane proteins followed by scintillation counting of gel slices and autoradiography showed that the polypeptides of molecular weights 28000, 23000 and 19000 were phosphorylated, and 32P from [gamma-32P]ATP having been incorporated into serine residues of the substrate proteins. Phosphorylation of purified myelin was Mg2+-dependent, was optimal at pH 6.5 and was not stimulated by adenosine 3',5'-monophosphate. We found that proteins other than those in myelin, such as phosvitin, casein, protamine and histones, can also act as a substrate for the membrane associated kinase. Muscle protein kinase inhibitor had no effect on the endogenous phosphorylation of myelin proteins or on the phosphorylation of phosvitin by peripheral nerve myelin protein kinase. However, the phosphorylation of histone by peripheral nerve myelin protein kinase was inhibited by the protein kinase inhibitor. After washing the membrane with 150 mM KCl the protein kinase that utilizes histone as substrate was found in the supernatant. In contrast, the endogenous phosphorylation of membrane proteins or the phosphorylation of phosvitin by the membrane associated kinase was not affected by washing. From these findings we conclude that at least two protein kinase systems exist in purified peripheral nerve myelin. One system is not inhibited by muscle kinase inhibitor, is tightly bound to the membrane and utilizes as its receptor proteins either exogenous phosvitin or endogenous membrane proteins. The second system is inhibited by muscle kinase inhibitor, is removable from the membrane and utilizes histones as its receptor proteins.

Adenosine Triphosphate↗

PubMed1977

The binding of calcium to a salivary phosphoprotein, protein C, and comparison with calcium binding to protein A, a related salivary phosphoprotein.

The binding of Ca2+ to a salivary phosphoprotein, protein C, was studied by equilibrium dialysis. In 5mM-Tris/HCl buffer, pH 7.5, protein C bound 190 nmol of Ca2+/mg of protein. The apparent dissociation constant, K, was determined to be 1.9 x 10(-4)M and the binding of Ca2+ to the protein was non-co-operative. The binding of Ca2+ to protein C apparently depends on groups which ionize above pH 5.0. Ca2+ binding decreased with increased concentration of the dialysis buffer and on addition of SrCL2, MgCl2 and MnCl2 to the dialysis buffer. Digestion of protein C with trypsin or collagenase or heating of the protein to 60 degrees or 100 degrees C had little or no effect on the Ca2+ binding. Digestion of protein C with alkaline phosphatase caused a decrease in the amount of protein-bound Ca2+. This was also found for another salivary phosphoprotein, protein A. In the absence of Ca2+ the S020,w for protein C was 1.29 S and in the presence of Ca2+ it was 1.46S. Ca2+ may cause a conformational change in the protein or an aggregation of the protein molecules. No conformational changes of protein C in the presence of Ca2+ could be detected by circular dichroism or nuclear magnetic resonance.

Calcium↗

PubMed2025

Uncoupling protein production from growth: different strategies for intracellular and secreted proteins in yeast.

BACKGROUND: Precision fermentation offers a sustainable alternative production route for proteins but still suffers from moderate productivities and low yields. Especially compared to biomass yields, recombinant protein yields on substrate are very low. Uncoupling recombinant protein production from growth would allow higher product yields, but requires that productivity is maintained. So far, two-phase production processes mostly rely on inducers to activate recombinant protein production after an initial growth phase, e.g., a change in carbon source. On large scale, specific growth rates can be controlled by nutrient availability, and we aim to use this as trigger to uncouple recombinant protein production from growth. RESULTS: We investigated the correlation between low specific growth rates (0.02 h- 1 < µ < 0.1 h- 1) and specific recombinant protein production rates, both for intracellularly accumulating and secreted proteins. By comparing two differently regulated promoters, the strong, constitutive PTEF1 and stress-induced PHSP12, we show that recombinant protein production rates and yields in Saccharomyces cerevisiae can be partially uncoupled from growth. The optimal strategy thereby differs for intracellular and secreted production. The PHSP12 resulted in increased product yields of intracellular protein at very low growth rates, including a 10-fold increase in intracellular protein titer, while titers remained virtually constant for the benchmark PTEF1. The PTEF1 on the other hand led to increased protein secretion rates and efficiencies at lower specific growth rates cumulating in higher extracellular protein titers. CONCLUSION: Our results demonstrate that promoter selection plays a critical role in production performance under slow growing conditions. Moreover, it highlights that optimising intracellular and extracellular recombinant protein production requires distinct, strategy-specific approaches.

Saccharomyces cerevisiae↗

PubMed2026

Protein isolation markedly enhances in vitro digestibility, nutritional quality, and bioactivity of fungal mycelial proteins.

Fungal mycelial proteins are promising sustainable protein sources, yet their nutritional utilization is often limited by structural constraints. This study systematically evaluated the effects of protein isolation on the proteomic composition, gastrointestinal digestion behavior, amino acid utilization, and bioactivity of Pleurotus citrinopileatus mycelial proteins. Quantitative proteomics identified 3591 proteins, of which 3374 were shared between mycelial flour (PCMF) and protein isolate (PCMPI), indicating that PCMPI primarily represents the soluble proteome fraction. In vitro digestion revealed that PCMPI exhibited significantly higher digestibility (93.98%) than PCMF (42.98%) (p < 0.05), reaching levels comparable to whey protein isolate. Enhanced enzymatic accessibility in PCMPI promoted rapid peptide generation during the gastric phase and efficient amino acid release during the intestinal phase, resulting in higher peptide (634.76 mg/g) and free amino acid levels (341.69 mg/g) at the digestion endpoint. Consequently, PCMPI achieved a balanced amino acid profile with a PDCAAS of 1.0. Moreover, its digestion products exhibited stronger antioxidant activity (IC₅₀ = 8.36 mg/mL) and ACE inhibitory activity (IC₅₀ = 15.65 mg/mL) compared with PCMF. Mechanistically, protein isolation disrupted the cell wall matrix, shifting digestion from a structure-limited to an accessibility-driven regime. Collectively, these findings demonstrate that protein isolation markedly enhances the digestibility, nutritional quality, and functional potential of mycelial proteins, supporting their application as high-value sustainable protein ingredients.

Digestion↗

PubMed2026

DPAS-Graph: adaptive spatial-feature relation learning for spatial RNA-to-protein prediction and virtual protein profiling.

Paired spatial multi-omics provides a supervised basis for learning RNA-protein correspondence in situ, but predicting protein abundance from spatial transcriptomic data alone remains challenging across tissue contexts and protein panels. Here, we present DPAS-Graph, an adaptive relation-learning framework for spatial RNA-to-protein prediction. Rather than directly merging spatial proximity and transcriptomic similarity as fixed graph priors, DPAS-Graph represents them as two relation channels on a shared edge support and updates their contributions during representation learning for protein prediction. Its Niche-Coupled Field Encoder combines layer-wise edge-relation modeling, intra-branch relation refinement, and cross-branch residual correction to learn spot representations for protein abundance prediction. In a leave-one-dataset-out benchmark across seven paired spatial multi-omics datasets, DPAS-Graph achieved lower aggregate prediction errors and improved spot-level agreement of protein expression profiles, with gains mainly reflected in error-based metrics and PCC-Spot. Spatial autocorrelation and protein-derived domain agreement analyses were further used to characterize the spatial behavior of the predicted protein maps. When applied to external RNA-only spatial sections, DPAS-Graph generated qualitatively interpretable marker-level virtual protein maps, illustrating its use as a complementary tool for protein-level interpretation of transcriptomics-only spatial data.

RNA↗

PubMed2025

STUPPIT is a proximity labeling tool for labeling intermediary proteins that bridge two non-interacting proteins.

Decoding the complexities of signaling pathways is fundamental for deciphering the mechanisms underlying tissue development, homeostasis, and disease pathogenesis. Proximity labeling tools have been instrumental in identifying upstream or downstream effectors of specific proteins within signaling pathways. However, currently, there are no tools available to directly label and capture intermediary proteins that bridge two non-interacting proteins. Here, we developed Split-TurboID and PUP-IT based Protein Identification Tool (STUPPIT), a novel method combining split-TurboID and PUP-IT to biotinylate intermediary proteins of two non-interacting proteins through a two-step enzymatic reaction. STUPPIT was validated using three well-characterized protein triads, including YAP1/AMOT/β-actin, YAP1/LATS1/MOB1A, and β-catenin/α-catenin/β-actin using HEK293T human cell lines. Combining STUPPIT and proteomics, we identified novel intermediary proteins including ERC1 and USP7, which interacted both with β-catenin and SMAD4, key components of the Wnt and BMP signaling pathways. In conclusion, STUPPIT represents a powerful tool for labeling and capturing intermediary proteins between non-interacting partners, offering new insights into protein-protein interactions and advancing signal transduction research.

Humans↗

PubMed1977

Interactions between "fever" proteins and normal serum proteins in febrile cancer patients.

When analyzed by cationic discontinuous electrophoresis in urea-containing polyacrylamide gels, plasma or serum from febrile individuals contains trace quanitites of five protein bands that are not recognizable in the blood of normal individuals. These proteins appear and disappear in parallel in sequential samples. Cerebrospinal fluid from febrile and nonfebrile individuals contains a protein band that is electrophoretically identical with only one of these proteins. Since the trace proteins migrate, in urea-containing polyacrylamide gel electrophoresis, as if they has molecular size of less than or equal to30,000 daltons, their absence from cerebrospinal fluid implies the existence, in vivo, of interactions between them and other serum proteins. Under nondissociating conditions, four of the bands appear to circulate in physical interaction with one another. In molecular sieve chromatography at neutral pH in lipid-free sera, the trace proteins have an approximate molecular size of 165,000 daltons; in lipemic sera they have a molecular weight of larger than or equal to200,000 daltons. Their behavior in gel filtration and in ion-exchange chromatography excludes extensive interaction with any of the following: immunoglobulin M, immunoglobulin G, alpha2-macroglobulin, haptoglobin, and albumin. Interactions between these and other serum proteins are reduced by high concentrations of urea and by low PH. The mechanisms responsible for the observed protein-protein associations would appear to include electrostatic attraction, hydrogen bonding, and weak hydrophobic interaction.

Blood Proteins↗

PubMed2025

Large Quantities of Bacterial DNA and Protein in Common Dietary Protein Source Used in Microbiome Studies.

Diet has been shown to greatly impact the intestinal microbiota. To understand the role of individual dietary components, defined diets with purified components are frequently used in diet-microbiota studies. Defined diets frequently use purified casein as the protein source. Previous work indicated that casein contains microbial DNA potentially impacting results of microbiome studies. Other diet-based microbially derived molecules that may impact microbiome measurements, such as proteins detected by metaproteomics, have not been determined for casein. Additionally, other protein sources used in microbiome studies have not been characterized for their microbial content. We used metagenomics and metaproteomics to identify and quantify microbial DNA and protein in a casein-based defined diet to better understand potential impacts on metagenomic and metaproteomic microbiome studies. We further tested six additional defined diets with purified protein sources with an integrated metagenomic-metaproteomic approach and found that contaminating microbial protein is unique to casein within the tested set as microbial protein was not identified in diets with other protein sources. We also illustrate the contribution of diet-derived microbial protein in diet-microbiota studies by metaproteomic analysis of stool samples from germ-free mice (GF) and mice with a conventional microbiota (CV) following consumption of diets with casein and non-casein protein. This study highlights a potentially confounding factor in diet-microbiota studies that must be considered through evaluation of the diet itself within a given study.

Animals↗

PubMed2026

Conserved protein folds underpin the diversification of secreted proteins in a fungal pathogen.

BACKGROUND: During host colonization, fungal plant pathogens secrete effector-like proteins that alter host cell physiology and target plant-associated microbes. However, rapid evolution and low sequence conservation hinder the study and characterization of these proteins. The fungus Zymoseptoria passerinii infects Hordeum spp. and includes lineages adapted to wild and domesticated barley. To date, the evolution of effector-like proteins in this species has not been addressed. RESULTS: We combined multiple structure-based and network analyses to unravel the secretome of Z. passerinii. We first compared AlphaFold2 and ESMFold predictions to establish the baseline for structural analyses. We identified 72 structural clusters in the secretome, revealing fold-level relationships across divergent sequences. We showed that effector-like proteins with predicted host immune-interfering functions evolved from a limited group of protein folds, whereas proteins with predicted antimicrobial properties were distributed across fold groups. Physicochemical comparisons indicate that putative antimicrobial effectors predominantly emerged through amino acid replacements on common effector-enriched scaffolds in Z. passerinii, reconfiguring surface charge and electrostatics. We analyzed intra- and interspecific variation in selected effector-enriched families by comparing Z. passerinii proteins and homologs across the genus Zymoseptoria. We describe constrained core folds, with local variation in loop and surface-exposed regions, consistent with fold stability while still enabling protein diversification. We further report that putative antimicrobial effector homologs are broadly distributed across the genus despite sequence divergence. CONCLUSIONS: The secretome of Z. passerinii is organized around common structural folds that support diverse biological roles, including host manipulation and host-associated microbial interactions. Conserved scaffolds combined with surface and physicochemical variation likely contribute to rapid adaptive evolution of effector-like proteins in Z. passerinii.

Fungal Proteins↗

PubMed2026

Decoding protein signatures and protein interactions in oral potentially malignant disorders: a systematic review and network analysis.

BACKGROUND: Proteomic profiling offers thorough insights into protein structure and function, as well as it acts as an essential approach for analyzing molecular changes at the tissue level. However, because of the proteome's diversity and dynamic nature, biomarker discovery remains challenging. By combining proteomics with bioinformatics, the level of understanding in relation to molecular interactions and disease processes can be improved. Through an integrative approach, few limitations can be addressed, thereby promoting proteomic profiling for the discovery of new therapeutic targets and novel biomarkers for a variety of disorders. AIM: To identify differentially expressed protein markers and their key molecular pathways associated with Oral Potentially Malignant Disorders. METHODS: Systematic Review was conducted following the PRISMA guidelines and the protocol registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the registration ID number CRD42024557545. A comprehensive literature review was performed using electronic databases, yielding 12,797, studies from which 15 eligible articles were selected. The Newcastle-Ottawa Scale was used to assess the risk of bias. Vote counting was performed to identify proteins reported in more than one study. A bipartite network was constructed using Cytoscape to identify shared and disease-specific protein markers. Lesion-wise protein-protein interaction networks were generated using STRING and analysed in Cytoscape to identify highly interconnected hub proteins, and pathway enrichment analysis for these hubs was performed using Reactome. RESULTS: A total of fifteen studies (Leukoplakia (LK) - n = 1, Proliferative Verrucous Leukoplakia (PVL) - n = 2, Oral Submucous Fibrosis (OSMF) - n = 7, and Oral Lichen Planus (OLP) - n = 5) were included. The Newcastle-Ottawa Scale was used to evaluate methodological quality and the quality of studies included in this systematic review was high for 4 articles and moderate in the remaining 11. The most commonly employed technique was mass spectrometry. A total of 318 candidate proteins (LK - 14, PVL - 82, OSMF - 172, and OLP - 50) were identified across the oral potentially malignant disorders. Key markers identified through vote counting included ERO1A, NUCB1, RHOA, and IL36A for PVL; LUM, KRT1, KRT9, ALB, and VIM for OSMF; and ALB, LYZ, HP, HBB, and AMY1A for OLP. The bipartite network showed that OSMF and OLP shared the highest number of proteins, indicating the strongest overlap among lesions. Network analysis further highlighted distinct hub proteins for each lesion: for LK- AMY1A, AMY1B and APOA1; for PVL- CFL1, RHOA and CDC42; for OSMF- HSP90AA1, ENO1 and SERPINA1; and for OLP- HP, B2M, and ORM1. Lesion-specific pathway enrichment revealed that LK was associated with epithelial differentiation, PVL with oncogenic signaling, OSMF with stress-driven fibrosis, and OLP with immune-mediated inflammation. CONCLUSIONS: Proteomic expression offers insights into disease pathogenesis by identifying important molecular changes across OPMDs. However, the majority of biomarkers are still in the exploratory stage due to the considerable variation in lesion types, sample sources, proteomic techniques, and reporting systems. In order to create reliable and clinically applicable biomarkers, future studies should concentrate on combining multi-omics techniques with large-scale, standardized cohorts.

Humans↗

PubMed2026

Comparison of Protein Coronas and Internalized Cell Surface Proteins of Positive and Negative Liposomes.

Positive nanoparticles have often a higher uptake than neutral and negative nanoparticles. This is usually attributed to electrostatic interactions with negatively charged proteoglycans on the cell membrane. However, upon contact with serum, nanoparticles adsorb a biomolecule corona and tend toward neutrality, suggesting that electrostatic interactions alone cannot explain the different uptake. Here, we used oppositely charged liposomes as an example to explore at a fundamental level why positive nanoparticles usually show a higher uptake than the negative ones. Two proteomic-based approaches were combined to compare their protein coronas and the cell surface proteins involved in their internalization. The results showed that the higher uptake of the positive liposomes used for this study could not be simply explained by the involvement of specific corona proteins and dominating cell surface proteins. Instead, small differences in the abundances of a large number of corona proteins and cell surface proteins were observed, including multiple low-abundance proteins. Importantly, the positive liposomes had higher uptake than the negative liposomes only when added to cells in the presence of serum, suggesting that the higher uptake likely resulted from the observed subtle differences in their corona and the collective contribution and interactions with multiple cell surface proteins.

Liposomes↗

PubMed1976

Influence of drugs and chemicals upon hepatic enzymes and proteins. II. The effects of various barbiturates on the induction and reduction of hepatic cytoplasmic organic anion-binding proteins.

The effects of seven barbiturates (phenobarbital, three N-phenylbarbiturates and three N-cyclohexylbarbiturates) on the hepatic cytoplasmic organic anion-binding proteins, Y and Z, were investigated in an attempt to observe the structure-activity relationship of baributrates to induction and reduction of these two proteins. Sulfobromophthalein (BSP) was fully bound by the Y and Z proteins at ten minutes of mixing with the 10,5000 X g supernate. In low concentrations of BSP, saturation of binding of BSP by the Z protein was very low, and with increasing concentration, BSP-binding by the Z protein increased rapidly. The Y protein bound BSP sufficiently even in low concentrations of the dye. BSP-binding capacity of the Yprotein was increased by phenobarbital, phetharbital and bucolome, and decreased by one of the N-phenylbarbiturates. BSP-binding capacity of the Zprotein tended to be decreased by phenobarbital and phetharbital, but to be increased by bucolome. The other N-phenyl- and N-cyclohexylbarbiturates had no effect on the binding capacities of the two proteins. From these results it was concluded that the regulation by the barbiturates of cytoplasmic proteins is different from that of the microsomal enzymes, and that both type and structural relation are important in the induction and reduction of the Y and Z proteins.

Animals↗

PubMed2026

Uncovering viral protein acquisition events and human-specific folds with pairwise comparisons of predicted protein structures.

Pairwise sequence comparisons are at the center of molecular evolutionary analyses. However, viral pairwise comparisons are challenging because extreme mutation rates and evolutionary pressure cause genomes to diverge rapidly, limiting detectable sequence similarity to fewer than 3% of virus pairs. To overcome these limitations, we compared viruses based on structural similarity, using predicted protein structures from ColabFold and Foldseek to define protein fold clusters. We represented each virus genome by its protein structural content. Pairwise similarities between viruses were then quantified using the Jaccard index based on the presence or absence of protein fold clusters. Using a recently established viral protein fold database, we compared all pairs of eukaryotic viruses in RefSeq. This approach increased the proportion of comparable viral genome pairs from 2.4% to 16.5%. Using this protein-fold representation of viruses, we were able to accurately predict viral families with an average sensitivity of 85.9%. Investigation of viral families showing limited sensitivity with this approach uncovered a laterally transferred structural cluster (Rep/NS1) broadly shared across diverse viral families and found in the avian lineage of adenoviruses. Sequence homology suggests that this Rep was acquired from Parvoviridae, but the protein is mutant in the ATPase active site, indicating possible exaptation toward a purely DNA-binding function. In Gammapapillomaviruses, several E4 clusters were associated with human tropism. In summary, by representing viruses with structural protein clusters, we can classify highly divergent viruses, trace lateral gene transfer, and uncover features associated with viral host range.

Humans↗

PubMed1976

Structural proteins of polyoma virus: proteolytic degradation of virion proteins by exogenous and by virion-associated proteases.

A model has previously been proposed for the genetic relatedness of the structural proteins of polyoma virus, based upon similarities in the peptide maps of the major capsid protein VP1 with the virion proteins VP2 and VP3. Newer evidence suggests that this model is incorrect, and that protein VP1 is a product of one viral gene and that the multiple components of VP2 and VP3 are products of a second viral gene. Two-dimensional peptide maps of several preparations of polyoma purified separately from four separate infected-cell lysates has shown a variable content of VP1 peptides in proteins VP2 and VP3, with some preparations being free of detectable VP1 material in VP2 and VP3. An alternative explanation for the presence of VP1 peptides in the regions of VP2 and VP3 of some polyoma preparations involves the cleavage of proteins of polyoma virions during exposure to proteolytic enzymes in lysates of infected cells or to endogenous proteolytic activity of virions. Prolonged incubation of infected-cell lysates at 37 degrees C leads to an increase in the amount of 86,000-dalton dimer of VP1, a decrease in the relative amount of VP1, a decrease in or a loss of the lower band of VP2, and the appearance of a new major protein band of approximately 29,000 daltons. Two-dimensional peptide maps of the new 29,000-dalton protein show that it contains some VP1 peptides, indicating that this protein is derived from proteolytic cleavage of VP1. In addition, extensively purified polyoma virus contains a proteolytic activity that can be activated during disruption of the virus with 0.2 M Na2CO3-NaHCO3 (pH 10.6) in the presence of 5 X 10(-3) M dithiothreitol.

Dithiothreitol↗