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Chain registry and load-dependent conformational dynamics of collagen.

ABSTRACT: Degradation of fibrillar collagen is critical for tissue maintenance. Yet, understanding collagen catabolism has been challenging partly due to a lack of atomistic picture for its load-dependent conformational dynamics, as both mechanical load and local unfolding of collagen affect its cleavage by matrix metalloproteinase (MMP). We use molecular dynamics simulation to find the most cleavage-prone arrangement of ? chains in a collagen triple helix and find amino acids that modulate stability of the MMP cleavage domain depending on the chain registry within the molecule. The native-like state is mechanically inhomogeneous, where the cleavage site interfaces a stiff region and a locally unfolded and flexible region along the molecule. In contrast, a triple helix made of the stable glycine-proline-hydroxyproline motif is uniformly flexible and is dynamically stabilized by short-lived, low-occupancy hydrogen bonds. These results provide an atomistic basis for the mechanics, conformation, and stability of collagen that affect catabolism.

SUBMITTER: Teng X

PROVIDER: S-EPMC4130245 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Chain registry and load-dependent conformational dynamics of collagen.

Teng Xiaojing X Hwang Wonmuk W

Biomacromolecules 20140707 8

Degradation of fibrillar collagen is critical for tissue maintenance. Yet, understanding collagen catabolism has been challenging partly due to a lack of atomistic picture for its load-dependent conformational dynamics, as both mechanical load and local unfolding of collagen affect its cleavage by matrix metalloproteinase (MMP). We use molecular dynamics simulation to find the most cleavage-prone arrangement of α chains in a collagen triple helix and find amino acids that modulate stability of t ...[more]

PMID: 24964130

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