Chain registry and load-dependent conformational dynamics of collagen. Academic Article

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.

authors

• Hwang, Wonmuk

published proceedings

• Biomacromolecules

author list (cited authors)

• Teng, X., & Hwang, W.

citation count

• 8

complete list of authors

• Teng, Xiaojing||Hwang, Wonmuk

publication date

• August 2014

publisher

• American Chemical Society (ACS)  Publisher

published in

• Biomacromolecules  Journal

keywords

• Collagen
• Humans
• Hydrogen Bonding
• Matrix Metalloproteinases
• Models, Theoretical
• Molecular Dynamics Simulation
• Proline
• Protein Conformation

PubMed Central ID

• 24964130

Digital Object Identifier (DOI)

• 10.1021/bm500641f

start page

• 3019

end page

• 3029

volume

• 15

issue

• 8

URL

• http://dx.doi.org/10.1021/bm500641f