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Sci Rep. 2018 Sep 14;8(1):13809. doi: 10.1038/s41598-018-31937-x.

Proline provides site-specific flexibility for in vivo collagen.

Author information

1
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
2
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) im Forschungsverbund Berlin e.V., Campus Berlin-Buch, Robert-Rössle-Str 10, 13125, Berlin, Germany.
3
Northwestern University, 633 Clark St, Evanston, IL, 60208, USA.
4
Department of Biochemistry, University of Cambridge, Downing Site, Cambridge, CB2 1QW, UK.
5
University of Calgary, 2500 University Dr. NW, Calgary, Alberta, T2N 1N4, Canada.
6
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.
7
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. mjd13@cam.ac.uk.

Abstract

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.

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