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 α 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.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Teng X,Hwang W

doi

10.1021/bm500641f

subject

Has Abstract

pub_date

2014-08-11 00:00:00

pages

3019-29

issue

8

eissn

1525-7797

issn

1526-4602

journal_volume

15

pub_type

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