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At least 919 records · Page 51Linked to original sources
PubMed1998

Complete primary structure of two variant forms of human type XVIII collagen and tissue-specific differences in the expression of the corresponding transcripts.

We report on full-length human type XVIII collagen cDNAs that encode 1516- or 1336-residue alpha 1 (XVIII) chains. The two chains have different signal peptides and variant N-terminal non-collagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share 301 residues of their NC1 domains, a 688-residue highly interrupted collagenous portion, and a 312-residue C-terminal non-collagenous portion. Alternative splicing affecting a 43-residue stretch at the junction of the NC1 domain and the beginning of the collagenous portion was identified. The amino acid sequences of the human and previously characterized mouse alpha 1 (XVIII) chains exhibit an overall identity of 79%. The highest homology between these chains was observed in their last 184 residues, corresponding to the proteolytic fragment endostatin, which is capable of inhibiting endothelial cell proliferation, angiogenesis and tumor growth (O'Reilly, et al., Cell 88: 277-285, 1997). Northern analysis of several adult and fetal tissues with a probe for the NC1-493 variant revealed marked amounts of the corresponding 6.2 and 5.0 kb mRNAs in liver, while other tissues contained only faint or undetectable signals. Hybridizations with a probe specific for the NC1-303 variant virtually lacked the liver signal but revealed clear 5.6 and 4.5 kb bands in heart, kidney, placenta, prostate, ovaries, skeletal muscle and small intestine, and faint signals in several other tissues. Thus mRNAs for the long variant occur prominently in liver, while those for the short variant appear to be the major ones in the other tissues analyzed.

Adult↗
PubMed1991

Glycopeptidolipids from Mycobacterium fortuitum: a variant in the structure of C-mycoside.

Strains from the Mycobacterium fortuitum complex contain surface species-specific lipids allowing their precise identification. In M. fortuitum biovar. peregrinum two major glycopeptidolipids, of the C-mycoside type, were characterized by a combination of chemical analyses, NMR, and FAB mass spectrometry. Important information was obtained by mass spectrometry both on their molecular weight and on the peptide and saccharide sequences without any derivatization. The basic structure of the two compounds was shown to be [formula: see text] The disaccharide part linked O-glycosidically to alaninol was either 3,4-di-O-methyl-alpha-L-rhamnopyranosyl (1----2) 3,4-di-O-methyl-alpha-L-rhamnopyranoside (mycoside I) or 3-O-methyl-alpha-L-rhamnopyranosyl (1----2) 3,4-di-O-methyl-alpha-L-rhamnopyranoside (mycoside II). This is an unusual structure of a C-mycoside since neither 6-deoxytalose nor its derivatives are present. Moreover, the oligosaccharide part is linked to the alaninol residue instead of the allo-threonine.

Chromatography, Thin Layer↗
PubMed2005

Structure of allelic variants of subtype 5 of histone H1 in pea Pisum sativum L.

The pea genome contains seven histone H1 genes encoding different subtypes. Previously, the DNA sequence of only one gene, His1, coding for the subtype H1-1, had been identified. We isolated a histone H1 allele from a pea genomic DNA library. Data from the electrophoretic mobility of the pea H1 subtypes and their N-bromosuccinimide cleavage products indicated that the newly isolated gene corresponded to the H1-5 subtype encoded by His5. We confirmed this result by sequencing the gene from three pea lines with H1-5 allelic variants of altered electrophoretic mobility. The allele of the slow H1-5 variant differed from the standard allele by a nucleotide substitution that caused the replacement of the positively charged lysine with asparagine in the DNA-interacting domain of the histone molecule. A temperature-related occurrence had previously been demonstrated for this H1-5 variant in a study on a worldwide collection of pea germplasm. The variant tended to occur at higher frequencies in geographic regions with a cold climate. The fast allelic variant of H1-5 displayed a deletion resulting in the loss of a duplicated pentapeptide in the C-terminal domain.

Alleles↗
PubMed1996

Altered glycosaminoglycan chain structure in a variant of the C2 mouse muscle cell line.

Experiments on the S27 cell line, a variant of the C2 mouse muscle cell line that shows reduced incorporation of 35SO4 into proteoglycans, suggest that proteoglycans play a role in the clustering of acetylcholine receptors, an early step in synaptogenesis. Thus, unlike the C2 line, S27 myotubes do not form acetylcholine receptor clusters on their surface in aneural cultures and form few clusters in response to agrin. We have examined the proteoglycans synthesized by S27 myotubes to define further the biochemical defect in these cells. Gel filtration analysis of radiolabeled proteoglycans synthesized by C2 and S27 myotubes shows that both cell types express a similarly polydisperse complement of proteoglycans. Both radiolabeled heparan sulfate proteoglycans and chondroitin/dermatan sulfate proteoglycans are reduced in S27 myotubes, with the chondroitin/dermatan sulfate proteoglycans showing a distinct reduction in size. The core protein of perlecan, a major proteoglycan species in muscle, was present in S27 cells and unaltered in electrophoretic mobility. Thus a principal deficiency in S27 cells appears to be a defect in glycosaminoglycan chain elongation.

Animals↗
PubMed2000

The spectral and thermodynamic properties of staphylococcal enterotoxin A, E, and variants suggest that structural modifications are important to control their function.

The superantigens staphylococcal enterotoxin A and E (SEA and SEE) can activate a large number of T-cells. SEA and SEE have approximately 80% sequence identity but show some differences in their biological function. Here, the two superantigens and analogues were characterized biophysically. SEE was shown to have a substantially higher thermal stability than SEA. Both SEA and SEE were thermally stabilized by 0.1 mM Zn(2+) compared with Zn(2+)-reduced conditions achieved using 1 mM EDTA or specific replacements that affect Zn(2+) coordination. The higher stability of SEE was only partly caused by the T-cell receptor (TCR) binding regions, whereas regions in the vicinity of the major histocompatibility complex class II binding sites affected the stability to a greater extent. SEE exhibited a biphasic denaturation between pH 5.0-6.5, influenced by residues in the TCR binding regions. Interestingly, enzyme-linked immunosorbent assay, isoelectric focusing, and circular dichroism analysis indicated that conformational changes had occurred in the SEA/E chimerical constructs relative to SEA and SEE. Thus, it is proposed that the Zn(2+) binding site is very important for the stability and potency of SEA and SEE, whereas residues in the TCR binding site have a substantial influence on the molecular conformation to control specificity and function.

Amino Acid Sequence↗
PubMed2000

Interaction of human alpha-Synuclein and Parkinson's disease variants with phospholipids. Structural analysis using site-directed mutagenesis.

alpha-Synuclein has been centrally implicated in neurodegenerative disease, and a normal function in developmental synaptic plasticity has been suggested by studies in songbirds. A variety of observations suggest the protein partitions between membrane and cytosol, a behavior apparently conferred by a conserved structural similarity to the exchangeable apolipoproteins. Here we show that the capacity to bind lipids is broadly distributed across exons 3, 4, and 5 (encoding residues 1-102). Binding to phosphatidylserine-containing vesicles requires the presence of all three exons, while binding to phosphatidic acid can be mediated by any one of the three. Consistent with a "class A2" helical binding mechanism, lipid association is disrupted by introduction of charged residues along the hydrophobic face of the predicted alpha-helix and also by biotinylation of conserved lysines (which line the interfacial region). Circular dichroism spectroscopy reveals a general correlation between the amount of lipid-induced alpha-helix content and the degree of binding to PS-containing vesicles. Two point mutations associated with Parkinson's disease have little (A30P) or no (A53T) effect on lipid binding or alpha-helicity. These results are consistent with the hypothesis that alpha-synuclein's normal functions depend on an ability to undergo a large conformational change in the presence of specific phospholipids.

Cloning, Molecular↗
PubMed2026

TriosCompass: a snakemake workflow for integrated detection of SNVs, indels, STRs, and structural de novo variants in parent-child trios.

MOTIVATION: The accurate and sensitive identification of de novo variants, which are unique to an individual and not found in the parents' germlines, is critical for understanding the genetic basis of rare diseases, developmental disorders, and evolutionary processes. Existing de novo variant detection pipelines often lack the flexibility to handle multiple variant types, struggle with speed and reproducibility across computational environments, demand extensive manual configuration, or require bioinformatics expertise for downstream curation and analysis, limiting their scalability and usability for large genomic studies. Accordingly, there is a pressing need to better address these challenges. RESULTS: We introduce TriosCompass, an open-source Snakemake workflow that addresses these challenges by providing a modular, accelerated, and environmentally-configurable end-to-end solution for comprehensive de novo variant discovery. It integrates state-of-the-art tools into a reproducible framework, empowering researchers to discover novel genetic insights with greater efficiency and reliability. AVAILABILITY: TriosCompass is implemented as a Snakemake workflow and is freely available at https://github.com/NCI-CGR/TriosCompass_v2 or on Zenodo (10.5281/zenodo.17981062). SUPPLEMENTARY INFORMATION: Supplementary data is available on GitHub at https://github.com/NCI-CGR/TriosCompass_v2/tree/manuscript/report_dashboards. Supplementary methods on DeepTrio benchmark runs can be viewed at: https://github.com/NCI-CGR/TriosCompass_v2/blob/manuscript/TriosCompass_Supp_Methods_deeptrio_benchmark.md.

Software↗
PubMed1989

Alternative splicing of the neural cell adhesion molecule gene generates variant extracellular domain structure in skeletal muscle and brain.

Myotube mRNA isoforms of the neural cell adhesion molecule (N-CAM) contain a novel sequence block termed muscle-specific domain 1 (MSD1), which is inserted within the extracellular coding region. Here, we report a characterization of the genomic organization of MSD1 and its pattern of expression within cellular N-CAM RNA and polypeptide species. S1 nuclease protection analyses and sequence analysis of an N-CAM human genomic clone containing MSD1 sequences indicated that MSD1 is comprised of three discrete exons of 15, 48, and 42 bp, designated MSD1a, MSD1b, and MSD1c, respectively. Although the MSD1a exon was present in a small proportion of mRNAs from both brain and muscle cells, the entire MSD1 sequence occurred predominantly in mRNAs from differentiated myotube cells. In addition, antiserum raised to a synthetic, MSD1b-encoded peptide sequence was found to stain the cell surface of human skeletal myotubes in culture, whereas myoblasts, fibroblasts, and neural cells were negative. MSD1a, MSD1b, and MSD1c sequences thus arise collectively in N-CAM mRNA and polypeptide isoforms as a result of muscle tissue-specific and developmentally regulated alternative mRNA splicing events. In addition, the occurrence of brain and muscle mRNAs containing only MSD1a indicate that alternative splicing may occur within the MSD region itself to generate further diversity.

Amino Acid Sequence↗
PubMed1979

[Intraspecies features of variants in the structure of the arterial bed in dogs and their importance for hindlimb transplantation].

As a result of detailed studies of the dog anatomy, the authors have concluded that besides generally accepted subdivision of these animals into flabby, rough, strong, lean and gentle types, it is reasonable to subdivide them according to the type of their habitus (brachy-, meso- and dolichomorphous types). In 95 fresh and fixed anatomical preparations, peculiarities of topographic-anatomical relations and morphometric indices of magistral arteries and their large branches have been studied in the pelvic girdle and a free hind extremity in mongrel dogs according to the type of their habitus. In dogs of mesomorphous type of habitus, quantitative parameters of the diameter and length of magistral arterial trunks in the hind extremity, as a well as the distance between their branches occupy an intermediate place when comparing the animals of brachy- and dolichomorphous types. The authors have come to the conclusion that dogs of the mesomorphous type of habitus are the most suitable to perform experiments on transplantation of extremities and for modelling different pathophysiologic conditions in the organ.

Animals↗