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Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine.
Proc Natl Acad Sci U S A. 2000 Apr 11; 97(8):4273-8.PN

Abstract

Mutations resulting in replacement of one obligate Gly residue within the repeating (Gly-Xaa-Yaa)(n) triplet pattern of the collagen type I triple helix are the major cause of osteogenesis imperfecta (OI). Phenotypes of OI involve fragile bones and range from mild to perinatal lethal. In this study, host-guest triple-helical peptides of the form acetyl-(Gly-Pro-Hyp)(3)-Zaa-Pro-Hyp-(Gly-Pro-Hyp)(4)-Gly-Gly-amide are used to isolate the influence of the residue replacing Gly on triple-helix stability, with Zaa = Gly, Ala, Arg, Asp, Glu, Cys, Ser, or Val. Any substitution for Zaa = Gly (melting temperature, T(m) = 45 degrees C) results in a dramatic destabilization of the triple helix. For Ala and Ser, T(m) decreases to approximately 10 degrees C, and for the Arg-, Val-, Glu-, and Asp-containing peptides, T(m) < 0 degrees C. A Gly --> Cys replacement results in T(m) < 0 degrees C under reducing conditions but shows a broad transition (T(m) approximately 19 degrees C) in an oxidizing environment. Addition of trimethylamine N-oxide increases T(m) by approximately 5 degrees C per 1 M trimethylamine N-oxide, resulting in stable triple-helix formation for all peptides and allowing comparison of relative stabilities. The order of disruption of different Gly replacements in these peptides can be represented as Ala </= Ser < CPO(red) < Arg < Val < Glu </= Asp. The rank of destabilization of substitutions for Gly in these Gly-Pro-Hyp-rich homotrimeric peptides shows a significant correlation with the severity of natural OI mutations in the alpha1 chain of type I collagen.

Authors+Show Affiliations

Department of Biochemistry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 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, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10725403

Citation

Beck, K, et al. "Destabilization of Osteogenesis Imperfecta Collagen-like Model Peptides Correlates With the Identity of the Residue Replacing Glycine." Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 8, 2000, pp. 4273-8.
Beck K, Chan VC, Shenoy N, et al. Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine. Proc Natl Acad Sci U S A. 2000;97(8):4273-8.
Beck, K., Chan, V. C., Shenoy, N., Kirkpatrick, A., Ramshaw, J. A., & Brodsky, B. (2000). Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine. Proceedings of the National Academy of Sciences of the United States of America, 97(8), 4273-8.
Beck K, et al. Destabilization of Osteogenesis Imperfecta Collagen-like Model Peptides Correlates With the Identity of the Residue Replacing Glycine. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4273-8. PubMed PMID: 10725403.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine. AU - Beck,K, AU - Chan,V C, AU - Shenoy,N, AU - Kirkpatrick,A, AU - Ramshaw,J A, AU - Brodsky,B, PY - 2000/3/22/pubmed PY - 2000/5/20/medline PY - 2000/3/22/entrez SP - 4273 EP - 8 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 97 IS - 8 N2 - Mutations resulting in replacement of one obligate Gly residue within the repeating (Gly-Xaa-Yaa)(n) triplet pattern of the collagen type I triple helix are the major cause of osteogenesis imperfecta (OI). Phenotypes of OI involve fragile bones and range from mild to perinatal lethal. In this study, host-guest triple-helical peptides of the form acetyl-(Gly-Pro-Hyp)(3)-Zaa-Pro-Hyp-(Gly-Pro-Hyp)(4)-Gly-Gly-amide are used to isolate the influence of the residue replacing Gly on triple-helix stability, with Zaa = Gly, Ala, Arg, Asp, Glu, Cys, Ser, or Val. Any substitution for Zaa = Gly (melting temperature, T(m) = 45 degrees C) results in a dramatic destabilization of the triple helix. For Ala and Ser, T(m) decreases to approximately 10 degrees C, and for the Arg-, Val-, Glu-, and Asp-containing peptides, T(m) < 0 degrees C. A Gly --> Cys replacement results in T(m) < 0 degrees C under reducing conditions but shows a broad transition (T(m) approximately 19 degrees C) in an oxidizing environment. Addition of trimethylamine N-oxide increases T(m) by approximately 5 degrees C per 1 M trimethylamine N-oxide, resulting in stable triple-helix formation for all peptides and allowing comparison of relative stabilities. The order of disruption of different Gly replacements in these peptides can be represented as Ala </= Ser < CPO(red) < Arg < Val < Glu </= Asp. The rank of destabilization of substitutions for Gly in these Gly-Pro-Hyp-rich homotrimeric peptides shows a significant correlation with the severity of natural OI mutations in the alpha1 chain of type I collagen. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/10725403/Destabilization_of_osteogenesis_imperfecta_collagen_like_model_peptides_correlates_with_the_identity_of_the_residue_replacing_glycine_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&amp;pmid=10725403 DB - PRIME DP - Unbound Medicine ER -