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At least 19 recordsLinked to original sources
PubMed2025

The TaCEP15 peptide signaling cascade modulates primary root length and drought tolerance in wheat.

Drought stress poses an environmental challenge affecting crop yield. Small signaling peptides play crucial roles in the regulation of stress responses in plants. Here, we unveil that the TaCEP15 peptide interacts with the leucine-rich repeat receptor-like kinase TaCEPRL. Knockout of TaCEP15 or TaCEPRL increases primary root length and enhances drought tolerance in wheat. TaCEPRL interacts with and phosphorylates TaSnRK1α, leading to the degradation of TaSnRK1α. The presence of TaCEP15 intensifies the phosphorylation and degradation of TaSnRK1α. Consistently, overexpressing TaSnRK1α boosts primary root elongation and augments drought tolerance. In addition, we identify the transcription factor TabZIP9, which binds to the TaCEP15 promoter and suppresses its transcription. A-to-T substitution in the TaCEP15 promoter decreases the binding affinity of TabZIP9. As expected, transgenic plants with TabZIP9 knockout or overexpression exhibit noteworthy changes in primary root length and drought tolerance. Our findings shed light on the importance of the peptide signaling pathway in regulating primary root length and responding to drought stress in wheat.

Triticum↗
PubMed2026

Enhanced Production of Recombinant Thermophilic Xylanase X11P in Ogataea polymorpha via In-Silico Signal Peptide Discovery and Fed-Batch Fermentation.

Efficient secretion of heterologous proteins is essential for advancing yeast-based bioprocesses, yet signal peptide (SP) optimization in the thermotolerant methylotrophic yeast Ogataea polymorpha remains limited. This study integrates in-silico SP discovery, experimental validation, and bioprocess engineering to enhance secretion of the thermophilic xylanase X11P under sucrose-inducible expression. Genome-wide screening of 5184 O. polymorpha proteins using SignalP, Phobius, DeepLoc, WoLF PSORT, and ProP identified 11 high-confidence SP candidates. Comparative analysis with Komagataella phaffii endogenous proteins guided selection of seven SPs for experimental evaluation. Among these, the novel O. polymorpha α-mating factor-like peptide FUN_005010 exhibited strong secretion-promoting activity, with its prepro-sequence yielding the highest extracellular xylanase levels and outperforming the classical Saccharomyces cerevisiae α-MF. To evaluate industrial applicability, sucrose-based fermentation strategies were systematically optimized in a 5-L bioreactor. Controlled sucrose feeding and balanced C/N ratios were found to be critical for maximizing maltase (MAL) promoter-driven expression. A stepwise increasing sucrose feed combined with induction at 30°C enabled X11P titers up to 770 U/mL, representing a 15-fold improvement over shake-flask cultures. This work demonstrates that the combination of SP evaluation and optimized sucrose-inducible fed-batch operation significantly enhances X11P production in O. polymorpha. The identified FUN_005010-prepro SP and the refined process framework provide valuable tools for developing O. polymorpha as a high-performance industrial expression platform.

Fermentation↗
PubMed2026

Pinpointing genomic regions conferring herbicide tolerance in cassava via genome-wide association mapping.

Cassava (Manihot esculenta Crantz) is a tropical crop of major socioeconomic importance, whose productivity can be limited by sensitivity to herbicides used for weed management. This study aimed to perform a genome-wide association study (GWAS) in 194 cassava genotypes to identify genomic regions associated with tolerance to the herbicides mesotrione, S-metolachlor, and chloransulam-methyl. The evaluations performed at 3, 6, 9, 15, and 30 days after application (DAA) were used to characterize the temporal progression of phytotoxicity. Based on this analysis, the phenotype obtained at 9 days after application (PhytoX9DAA) was selected for genome-wide association analyses because it represented the period of greatest symptom expression and the highest discrimination among genotypes. GWAS analyses were performed using de-regressed BLUPs and the MLM, MLMM, and BLINK models, incorporating kinship (K) and population structure (Q) matrices. Significant markers were detected across multiple chromosomes, and the corresponding genomic windows contained candidate genes with functional annotations related to herbicide response. The predominant functional categories included membrane transport, channel activity, signal peptide processing, protein phosphorylation, cellular signaling, and metabolic regulation. Key candidate genes included Manes.02G151900 and Manes.02G152700 (chromosome 2), associated with transmembrane transport and signal peptide processing; Manes.09G060900 (chromosome 9), associated with protein kinase activity, ATP binding, and protein phosphorylation; and Manes.15G083800 and Manes.15G084000 (chromosome 15), associated with S-adenosylmethionine-dependent methyltransferase activity, membrane-related functions, and protein phosphorylation. These genes participate in biochemical pathways involved in cellular signaling, membrane transport, and metabolic regulation that may contribute to herbicide tolerance. Overall, the results demonstrate that herbicide tolerance in cassava is a quantitative and polygenic trait governed by numerous small-effect loci. The integration of cellular signaling, metabolic regulation, and membrane transport supports the physiological resilience of the species under chemical exposure, providing valuable insights for breeding strategies and marker-assisted selection.

Genome-Wide Association Study↗
PubMed2026

The transgenic Vip3A poplar plant confers high resistance against Hyphantria cunea Drury.

Poplar is severely damaged by Hyphantria cunea (fall webworm), which significantly reduces tree productivity. However, conventional pest management methods are largely ineffective against fall webworm infestation. In this study, we demonstrated that the Vip3A protein possesses high insecticidal activity against H. cunea by overexpressing a synthetic THI1-Vip3A gene in poplar plants. A dicot codon-optimized Vip3A gene, fused with the THI1 chloroplast signal peptide sequence, was chemically synthesized and introduced into the poplar cv. '741' genome via Agrobacterium-mediated transformation. PCR, RT-PCR, and ELISA analyses confirmed the integration and successful expression of the transgene at both the mRNA and protein levels. The Vip3A protein concentration in chloroplasts was approximately 4.8-fold higher than in the whole leaf extract, indicating that the Vip3A protein was successfully targeted to and accumulated within the chloroplasts by the THI1 signal peptide. Subsequently, four transgenic lines with high Vip3A expression were subjected to H. cunea infestation. Compared to wild-type plants, these four transgenic lines exhibited significantly higher resistance, resulting in pest mortality rates exceeding 95% and significantly reduced leaf damage. Together, these results indicate that Vip3A possesses high insecticidal activity against H. cunea. Therefore, transgenic THI1-Vip3A poplar plants can serve as valuable germplasm for breeding poplar cultivars with high resistance to H. cunea infestation.

Plants, Genetically Modified↗
PubMed1978

Coupled cell-free synthesis, segregation, and core glycosylation of a secretory protein.

mRNA from rat mammary glands 13-15 days post partum was translated in a wheat germ cell-free system either in the absence or in the presence of ribosome-denuded membranes prepared from isolated rough microsomes of dog pancreas. Newly synthesized alpha-lactalbumin was identified by immunoprecipitation with a monospecific rabbit antiserum against rat alpha-lactalbumin and was characterized by partial amino-terminal sequence determination and by lectin affinity chromatography. In the absence of membranes a presumably unglycosylated form of alpha-lactalbumin was synthesized that bound neither to concanavalin A-Sepharose nor to Ricinus communis lectin-agarose and that contained an amino-terminal signal peptide region comprising 19 amino acid residues. In the presence of membranes a processed form was synthesized that lacked the signal peptide portion and that had an amino-terminal sequence identical to that of mature alpha-lactalbumin. Furthermore, this processed form was found to be segregated, presumably within the microsomal vesicles, because it was resistant to post-translational proteolysis. It was also found to be glycosylated, and because it bound to concanavalin A-Sepharose, from which it could be eluted specifically by alpha-methyl mannoside, but not to R. communis lectin-agarose, it was presumably core-glycosylated. Processing, segregation, and core glycosylation were observed to proceed only when membranes were present during translation and not when they were added after translation.

Amino Acid Sequence↗
PubMed1979

Study of the precursors of ovine lactoproteins: primary structures of the 'signals' and enzymic processing of prelactoproteins by mammary microsomal membranes.

The radiolabelled primary translation products of ovine mammary mRNAs synthesized in a wheat germ cell-free system were isolated by immunoprecipitation and analysed by automated Edman degradation. The 3 'Ca-sensitive' caseins (alpha S1, alpha S2 and beta), kappa-casein, beta-lactoglobulin and alpha-lactalbumin were found to be synthesized as precursors with amino terminal extensions of 15, 21, 18 and 19 amino acid residues respectively. The extra pieces of these various lactoproteins are similar to 'signal' peptides of other secretory proteins in their length and hydrophobicity. The occurrence of an alanyl residue at the C-termini of the extra pieces of the 6 ovine prelactoproteins suggests that the mammary proteinase responsible for the cleavage of the signal peptides may have an elastase-like specificity. When mammary mRNAs were translated in a wheat germ cell-free system in the presence of mammary microsomal membranes, pre-beta-casein was converted into authentic beta-casein as demonstrated by amino terminal sequence analyses. Additionally, pre-beta-casein was post-translationally converted into authentic beta-casein by a specific proteinase(s) extracted from rough microsomes with Na deoxycholate.

Amino Acid Sequence↗
PubMed2024

Mapping Start Codons of Small Open Reading Frames by N-Terminomics Approach.

sORF-encoded peptides (SEPs) refer to proteins encoded by small open reading frames (sORFs) with a length of less than 100 amino acids, which play an important role in various life activities. Analysis of known SEPs showed that using non-canonical initiation codons of SEPs was more common. However, the current analysis of SEP sequences mainly relies on bioinformatics prediction, and most of them use AUG as the start site, which may not be completely correct for SEPs. Chemical labeling was used to systematically analyze the N-terminal sequences of SEPs to accurately define the start sites of SEPs. By comparison, we found that dimethylation and guanidinylation are more efficient than acetylation. The ACN precipitation and heating precipitation performed better in SEP enrichment. As an N-terminal peptide enrichment material, Hexadhexaldehyde was superior to CNBr-activated agarose and NHS-activated agarose. Combining these methods, we identified 128 SEPs with 131 N-terminal sequences. Among them, two-thirds are novel N-terminal sequences, and most of them start from the 11-31st amino acids of the original sequence. Partial novel N-termini were produced by proteolysis or signal peptide removal. Some SEPs' transcription start sites were corrected to be non-AUG start codons. One novel start codon was validated using GFP-tag vectors. These results demonstrated that the chemical labeling approaches would be beneficial for identifying the start codons of sORFs and the real N-terminal of their encoded peptides, which helps better understand the characterization of SEPs.

Open Reading Frames↗
PubMed2025

RRNPP quorum-sensing repertoires in the salivarius group genomes: overrepresentation and synchronous activation of SHP/Rgg systems in Streptococcus thermophilus.

UNLABELLED: In Bacillota, quorum sensing can be mediated by RRNPP regulators that are activated by autoinducing peptides (AIPs). In this study, we derived a hidden Markov model profile from a 3D-informed alignment to establish RRNPP repertoires for 527 genomes of streptococci in the salivarius group and identified probable AIPs. The salivarius group encompasses Streptococcus salivarius and Streptococcus vestibularis, which are part of the normal human oral microflora, and Streptococcus thermophilus, one of the most widely used bacteria in the dairy industry. We observed a large amount of plasticity in these repertoires, as well as profound differences among species. Notably, S. salivarius displayed an accumulation of ComR regulators, while S. thermophilus displayed an accumulation of Rgg regulators. The latter family included SHP-associated Rgg regulators, systems in which SHPs serve as AIPs; most of these regulators control the production of post-translationally modified peptides (RaS-RiPPs). Their level of richness contrasts with the genome reduction that accompanied S. thermophilus' adaptation to milk. We then used liquid chromatography-high resolution tandem mass spectrometry to analyze the activity of the eight most common SHP/Rgg systems by characterizing the SHPs and RaS-RiPPs found in the supernatants. We detected four SHPs and one RaS-RiPP that have never been seen before in S. thermophilus, and we showed that seven of the eight SHP/Rgg systems were functional. Finally, by simultaneously monitoring the amounts of both the SHPs and RaS-RiPPs, we demonstrated that the fates of these two peptide types differed during growth. SHP presence in the supernatant was transient, a pattern likely related to the peptides' signaling role. IMPORTANCE: Streptococcus thermophilus possesses an unusually high number of Rgg regulators, which are activated by SHP pheromones that control the production of RaS-RiPPs, peptides with cyclization motifs and growth inhibition properties. We conducted an in silico analysis of regulator repertoires across a wide range of strains; a subsequent experimental study revealed that the majority of the SHP/Rgg systems were functional. Employing an optimized liquid chromatography-high resolution tandem mass spectrometry protocol, we were able to better detect and follow SHP and RaS-RiPP accumulation. While RaS-RiPPs accumulated during growth, SHPs were only transiently present in the extracellular environment. This observation suggests that we could manipulate quorum sensing by adding SHPs to the growth medium and highlights the need to study the functions of the RaS-RiPPs.

Streptococcus thermophilus↗
PubMed2025

Efficient Expression of Oropouche Virus Nonstructural Proteins NSs and NSm.

Oropouche fever, a mosquito- or midge-borne emerging zoonotic disease endemic to South and Central America, manifests as a dengue-like acute febrile illness with occasional occurrences of meningitis or meningoencephalitis. The causative agent, Oropouche virus (OROV), belongs to the genus Orthobunyavirus within the family Peribunyaviridae. Its tripartite negative-sense RNA genome comprises small (S), medium (M), and large (L) segments, encoding structural N, Gn/Gc, and L proteins, respectively. Additionally, the S- and M-segments encode nonstructural proteins: NSs and NSm, which may act as virulence factors. OROV NSs functions as an interferon antagonist with an unknown mechanism, while the roles of OROV NSm remain elusive. This chapter introduces efficient expression systems for OROV NSm and NSs proteins. Validating the presence of a signal peptide at the N-terminus of NSm protein is essential for its expression. Furthermore, expressing OROV NSs protein independently of an RNA polymerase II promoter is crucial to prevent restricted gene expression, potentially caused by NSs inhibiting cellular RNA polymerase II, as observed in closely related bunyavirus NSs proteins. These protein expression strategies offer insights into the molecular characterization of OROV NSm and NSs proteins, facilitating a deeper understanding of their virulence mechanisms.

Viral Nonstructural Proteins↗
PubMed2026

Integrated LiP-MS and quantitative proteomics reveal coordinated alterations in protein conformation and expression across tumor and peritumoral regions in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) exhibits substantial molecular heterogeneity, yet protein-level alterations beyond abundance remain insufficiently characterized. Here, we integrated limited proteolysis mass spectrometry (Lip-MS) with 4D label-free quantitative proteomics to investigate conformational accessibility and protein abundance across tumor, peritumoral-near, and peritumoral-far tissues from HCC patients. Differential LiP peptides identified by both DDA and DIA corresponded to 725, 674, and 33 differentially conformed proteins in the Tumor vs. Peritumor-far, Tumor vs. Peritumor-near, and Peritumor-near vs. Peritumor-far comparisons, respectively. Quantitative proteomics identified 405, 365, and 4 differentially expressed proteins in the corresponding comparisons. Integrated analysis identified 488 and 469 conformation-specific altered proteins (CSAPs), which showed altered conformational accessibility without significant abundance changes, and 237 and 205 conformation-expression coupled proteins (CECPs) in the two tumor-involved comparisons. LiP peptide and protein abundance changes were positively correlated, with Spearman coefficients of 0.69-0.72, and more than 99% of CECPs showed concordant directions. Among them, 169 region-conserved CECPs (rcCECPs) were predominantly associated with metabolic and redox-related pathways. Protein-protein interaction analysis identified 30 hub rcCECPs. ACLY, ALDH18A1, GMPS, and DHX9 showed increased representative LiP peptide signals and protein abundance, elevated transcript expression in HCC, and associations with poorer overall survival. Peptide mapping further localized their differential LiP signals to specific sequence regions and annotated domains. Collectively, these findings provide an integrated view of regional conformational accessibility and protein abundance alterations in HCC and identify candidate proteins for further structural and functional investigation.

Humans↗
PubMed1979

Processing in vitro of placental peptide hormones by smooth microsomes.

Rough and smooth microsomes were prepared from ascites tumor cells, rat liver, and bovine adrenal cortex. Proteolytic removal of the signal peptide in pre-placental lactogen and asparagine-linked glycosylation of the alpha subunit of chorionic gonadotropin by these fractions were examined in mRNA-dependent lysates from ascites cells. Both processing steps were performed by smooth microsomes, which was unexpected because it has been presumed that only rough microsomes contain components for ribosomal binding. Thus smooth microsomes are apparently capable of interacting with polysomes bearing secretory nascent chains, and cleavage and asparagine-linked glycosylation activities are present in both rough and smooth endoplasmic reticulum.

Adrenal Cortex↗
PubMed1979

Initiation and processing in vitro of the primary translation products of guinea-pig caseins.

1. Guinea-pig caseins synthesized in a mRNA-directed wheat-germ cell-free protein-synthesizing system represent the primary translation products, even though they appear to be of lower molecular weight when analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis in parallel with caseins isolated from guinea-pig milk. 2. Identification of the N-terminal dipeptide of the primary translational product of caseins A, B and C and alpha-lactalbumin showed that all shared a common sequence, which was identified as either Met-Arg or Met-Lys. 3. Procedures utilizing methionyl-tRNAfMet or methionyl-tRNAMet in the presence or absence of microsomal membranes during translation provide a rapid method of distinguishing between N-terminal processing of peptides synthesized in vitro and other post-translational modifications (glycosylation, phosphorylation), which also result in a change in mobility of peptides when analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 4. The results demonstrate that guinea-pig caseins, in common with most other secretory proteins, are synthesized with transient N-terminal 'signal'-peptide extensions, which are cleaved during synthesis in the presence of microsomal membranes.

Animals↗
PubMed1978

Detection of prokaryotic signal peptidase in an Escherichia coli membrane fraction: endoproteolytic cleavage of nascent f1 pre-coat protein.

An inverted membrane vesicle fraction isolated from uninfected Escherichia coli and largely derived from the inner membrane has been shown to contain an endoproteolytic activity that cleaves nascent bacteriophage f1 pre-coat protein into two identifiable products. The electrophoretic mobility on sodium dodecyl sulfate/urea/polyacrylamide gels and the partial amino-terminal sequence of the larger fragment were indistinguishable from those of the mature phage coat protein. Partial amino-terminal sequence analysis showed that the smaller fragment corresponds to the amino-terminal "signal peptide" of f1 pre-coat protein. Cleavage occurred only if the membrane fraction was present during in vitro synthesis, and was not observed if it was added after completion of pre-coat protein synthesis. The cleavage reaction was strongly stimulated when the membrane fraction was present together with the nonionic detergent Nikkol. These results are consistent with and discussed in terms of the signal hyothesis.

Amino Acid Sequence↗
PubMed1979

Two processing steps in maturation of vitellogenin polypeptides in Drosophila melanogaster.

Synthesis of the three vitellogenin polypeptides (molecular weights of 44,000, 45,000, and 46,000) of Drosophila melanogaster has been analyzed in vivo and in a cell-free system. After labeling periods in vivo, the three vitellogenin polypeptides were made as the principal synthetic products of the female fat body. During a short (0.5 min) labeling period, they were identified as discrete species on two-dimensional gels. Two of the polypeptides have molecular weights of 45,000 and a third has a molecular weight of 44,000. After longer labeling periods (5-45 min) the three mature vitellogenins appeared. Both immunoprecipitation and peptide mapping confirmed that the species labeled at 0.5 min are immature forms of the vitellogenin polypeptides. In vitro translation of poly(A)-RNA from female fat body indicated another processing step in vitellogenin synthesis. Three polypeptides were obtained that were identified as precursors of the vitellogenins on the basis of immunoprecipitation and peptide mapping. Two of the translation products have a molecular weight of 46,000 and the third has a molecular weight of 45,000. Because the vitellogenins are secreted proteins, we interpret the higher molecular weight of the in vitro translation products as being due to signal peptides.

Adipose Tissue↗