Proline provides site-specific flexibility for in vivo collagen.

Autor: Chow WY; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) im Forschungsverbund Berlin e.V., Campus Berlin-Buch, Robert-Rössle-Str 10, 13125, Berlin, Germany., Forman CJ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.; Northwestern University, 633 Clark St, Evanston, IL, 60208, USA., Bihan D; Department of Biochemistry, University of Cambridge, Downing Site, Cambridge, CB2 1QW, UK.; University of Calgary, 2500 University Dr. NW, Calgary, Alberta, T2N 1N4, Canada., Puszkarska AM; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Rajan R; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Reid DG; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Slatter DA; Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK., Colwell LJ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Wales DJ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Farndale RW; Department of Biochemistry, University of Cambridge, Downing Site, Cambridge, CB2 1QW, UK., Duer MJ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. mjd13@cam.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Sep 14; Vol. 8 (1), pp. 13809. Date of Electronic Publication: 2018 Sep 14.
DOI: 10.1038/s41598-018-31937-x
Abstrakt: 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 13 C- 13 C correlation NMR spectroscopy on 13 C-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.
Databáze: MEDLINE
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