Conformational stability of the collagen triple helix affects its turnover and
determines tissue homeostasis. Although it is known that the presence of imino
acids (prolines or hydroxyprolines) confer stability to the molecule, little is known
regarding the stability of the imino-poor region lacking imino acids, which plays a
key role in collagen cleavage. In particular, there have been continuing debates about
the role of water in collagen stability. We addressed these issues using molecular
dynamics simulations on 30-residue long collagen triple helices, including a structure
that has a biologically relevant 9-residue imino-poor region from type III collagen
(Protein Data Bank ID: 1BKV). We characterized the conformational motion of the
molecule that differs between imino-rich and imino-poor regions using a torsional map
approach. At temperatures of 300 K and above, unwinding initiates at a common
cleavage site, the glycine-isoleucine bond in the imino-poor region. This provides
a linkage between previous observations that unwinding of the imino-poor region
is a requirement for collagenase cleavage, and that isolated collagen molecules are
unstable at body temperature. Unwinding of the imino-poor region is controlled by
dynamic water bridges between backbone atoms with average lifetimes on the order
of a few picoseconds, as the degree of unwinding strongly correlated with the loss
of water bridges, and unwinding could be either prevented or enhanced, respectively
by enforcing or forbidding water bridge formation. While individual water bridges
were short-lived in the imino-poor region, the hydration shell surrounding the entire
molecule was stable even at 330 K. The diameter of the hydrated collagen including the first hydration shell was about 14 Â, in good agreement with the experimentally
measured inter-collagen distances. These results elucidate the general role of water in
collagen turnover: water not only affects collagen cleavage by controlling its torsional
motion, but it also forms a larger-scale lubrication layer mediating collagen self-assembly.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/85997 |
| Date | 10 October 2008 |
| Creators | Mayuram Ravikumar, Krishnakumar |
| Contributors | Hwang, Wonmuk |
| Publisher | Texas A&M University |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Thesis, text |
| Format | electronic, born digital |
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