Proline provides site-specific flexibility for in vivo collagen.

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Forman, Chris J 
Bihan, Dominique 
Puszkarska, Anna M 
Rajan, Rakesh 

Fibrillar collagens have mechanical and biological roles, providing tissues with both tensile strength and cell binding sites which allow molecular interactions with cell-surface receptors such as integrins. A key question is: how do collagens allow tissue flexibility whilst maintaining well-defined ligand binding sites? Here we show that proline residues in collagen glycine-proline-hydroxyproline (Gly-Pro-Hyp) triplets provide local conformational flexibility, which in turn confers well-defined, low energy molecular compression-extension and bending, by employing two-dimensional 13C-13C correlation NMR spectroscopy on 13C-labelled intact ex vivo bone and in vitro osteoblast extracellular matrix. We also find that the positions of Gly-Pro-Hyp triplets are highly conserved between animal species, and are spatially clustered in the currently-accepted model of molecular ordering in collagen type I fibrils. We propose that the Gly-Pro-Hyp triplets in fibrillar collagens provide fibril "expansion joints" to maintain molecular ordering within the fibril, thereby preserving the structural integrity of ligand binding sites.

Amino Acid Sequence, Amino Acids, Animals, Collagen, Female, Fibrillar Collagens, Glycine, Hydroxyproline, Magnetic Resonance Spectroscopy, Mice, Mice, Inbred C57BL, Osteoblasts, Peptides, Proline, Protein Conformation, Sheep
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Springer Science and Business Media LLC
Biotechnology and Biological Sciences Research Council (BB/G021392/1)
European Commission (631609)
Engineering and Physical Sciences Research Council (EP/N035003/1)
Wellcome Trust (094470/Z/10/Z)
British Heart Foundation (None)
British Heart Foundation (None)
BBSRC, EPSRC, Raymond and Beverly Sackler Fund for Physics of Medicine, Wellcome Trust, ERC