NDLI: Osteogenesis imperfecta mutations lead to local tropocollagen unfolding and disruption of H-bond network

Content Provider	Royal Society of Chemistry (RSC)
Author	Buehler, Markus J. Redaelli, Alberto Gautieri, Alfonso Vesentini, Simone
Copyright Year	2012
Abstract	Osteogenesis imperfecta (OI), also known as “brittle bone disease”, is a rare genetic disorder of collagen tissues characterized by brittle bones and, in severe cases, prenatal death. Even though the macroscale consequences of the disease are well known, the effects of the mutations on the folding of collagen triple helix remain largely unknown. In this work we carry out metadynamics molecular simulations to estimate the effects of OI mutations on the folding of collagen triple helix, by quantifying the free energy changes as a function of the interchain distance, for all seven glycine substitutions known to lead to OI. We find that OI mutations lead to significant local unfolding in the vicinity of the mutation and that this phenomenon is more pronounced for mutations associated with the most severe OI phenotypes. We show that the mutation-induced unfolding leads to the disruption of the local interchain H-bonds, but the extent of the disruption is independent of the mutation type. We discuss our findings in the context of the three main OI mechanism models proposed in the literature, showing that the findings described here fit well in these models and, more importantly, could provide an important step towards a unified picture of OI aetiology.
Starting Page	3890
Ending Page	3896
Page Count	7
File Format	HTM / HTML PDF
ISSN	20462069
Volume Number	2
Issue Number	9
Journal	RSC Advances
DOI	10.1039/c2ra01047j
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Genetic disorder Collagen Osteogenesis imperfecta Mutation Metadynamics Glycine Osteogenesis Thermodynamic free energy
Content Type	Text
Resource Type	Article
Subject	Chemistry Chemical Engineering

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Osteogenesis imperfecta mutations lead to local tropocollagen unfolding and (2011)

Osteogenesis imperfecta mutations lead to local tropocollagen unfolding and disruption of H-bond network

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Treatment of osteogenesis imperfecta in adults.

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Osteogenesis imperfecta mutations lead to local tropocollagen unfolding and disruption of H-bond network

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