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Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders.
Hum Mutat. 2004 Oct; 24(4):330-7.HM

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15365990

Citation

Persikov, Anton V., et al. "Stability Related Bias in Residues Replacing Glycines Within the Collagen Triple Helix (Gly-Xaa-Yaa) in Inherited Connective Tissue Disorders." Human Mutation, vol. 24, no. 4, 2004, pp. 330-7.
Persikov AV, Pillitteri RJ, Amin P, et al. Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders. Hum Mutat. 2004;24(4):330-7.
Persikov, A. V., Pillitteri, R. J., Amin, P., Schwarze, U., Byers, P. H., & Brodsky, B. (2004). Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders. Human Mutation, 24(4), 330-7.
Persikov AV, et al. Stability Related Bias in Residues Replacing Glycines Within the Collagen Triple Helix (Gly-Xaa-Yaa) in Inherited Connective Tissue Disorders. Hum Mutat. 2004;24(4):330-7. PubMed PMID: 15365990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders. AU - Persikov,Anton V, AU - Pillitteri,Rian J, AU - Amin,Priyal, AU - Schwarze,Ulrike, AU - Byers,Peter H, AU - Brodsky,Barbara, PY - 2004/9/15/pubmed PY - 2005/4/1/medline PY - 2004/9/15/entrez SP - 330 EP - 7 JF - Human mutation JO - Hum Mutat VL - 24 IS - 4 N2 - 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. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/15365990/Stability_related_bias_in_residues_replacing_glycines_within_the_collagen_triple_helix__Gly_Xaa_Yaa__in_inherited_connective_tissue_disorders_ L2 - https://doi.org/10.1002/humu.20091 DB - PRIME DP - Unbound Medicine ER -