Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-14
pubmed:abstractText
A missense mutation leading to the replacement of one Gly in the (Gly-Xaa-Yaa)n repeat of the collagen triple helix can cause a range of heritable connective tissue disorders that depend on the gene in which the mutation occurs. Osteogenesis imperfecta results from mutations in type I collagen, Ehlers-Danlos syndrome type IV from mutations in type III collagen, Alport syndrome from mutations in type IV collagen, and dystrophic epidermolysis bullosa from mutations in type VII collagen. The predicted rates of substitutions by different amino acids for glycine in the alpha1(I), alpha2(I), alpha1(III), alpha5(IV), and alpha1(VII) chains (encoded by COL1A1, COL1A2, COL3A1, COL4A5, and COL7A1, respectively) were compared with missense mutations in those chains that have been observed to cause disease. The spectrum of amino acids replacing Gly was not significantly different from that expected for the alpha1(VII) chains, suggesting that any Gly replacement will cause disease. The distribution of residues replacing Gly was significantly different from that expected for all other collagen chains studied, with a particularly strong bias seen for alpha1(I) and alpha1(III) collagen chains. The bias did not correlate with the degree of chemical dissimilarity between Gly and the replacement residues, but in some cases a relationship was observed with the predicted extent of destabilization of the triple helix. For alpha1(III) collagen chains, the more destabilizing mutations were identified more often than expected. For alpha1(I), the most destabilizing residues, Val, Glu, and Asp, and the least destabilizing residue, Ala, were underrepresented. This bias supports the hypothesis that the level of triple-helix destabilization determines clinical outcome.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
330-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15365990-Amino Acid Substitution, pubmed-meshheading:15365990-Amino Acids, pubmed-meshheading:15365990-Collagen, pubmed-meshheading:15365990-Collagen Diseases, pubmed-meshheading:15365990-Collagen Type I, pubmed-meshheading:15365990-Collagen Type III, pubmed-meshheading:15365990-Collagen Type IV, pubmed-meshheading:15365990-Collagen Type VII, pubmed-meshheading:15365990-Epidermolysis Bullosa Dystrophica, pubmed-meshheading:15365990-Glycine, pubmed-meshheading:15365990-Humans, pubmed-meshheading:15365990-Mutation, Missense, pubmed-meshheading:15365990-Nephritis, Hereditary, pubmed-meshheading:15365990-Protein Denaturation, pubmed-meshheading:15365990-Protein Structure, Secondary, pubmed-meshheading:15365990-Protein Structure, Tertiary, pubmed-meshheading:15365990-Structure-Activity Relationship
pubmed:year
2004
pubmed:articleTitle
Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders.
pubmed:affiliation
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't