Proline provides site-specific flexibility for in vivo collagen
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 wel...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-09-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-018-31937-x |
| _version_ | 1818996044321521664 |
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| author | Wing Ying Chow Chris J. Forman Dominique Bihan Anna M. Puszkarska Rakesh Rajan David G. Reid David A. Slatter Lucy J. Colwell David J. Wales Richard W. Farndale Melinda J. Duer |
| author_facet | Wing Ying Chow Chris J. Forman Dominique Bihan Anna M. Puszkarska Rakesh Rajan David G. Reid David A. Slatter Lucy J. Colwell David J. Wales Richard W. Farndale Melinda J. Duer |
| author_sort | Wing Ying Chow |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T21:23:29Z |
| format | Article |
| id | doaj.art-eb22423885e3428eb990590955b04686 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:23:29Z |
| publishDate | 2018-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-eb22423885e3428eb990590955b046862022-12-21T19:26:13ZengNature PortfolioScientific Reports2045-23222018-09-018111310.1038/s41598-018-31937-xProline provides site-specific flexibility for in vivo collagenWing Ying Chow0Chris J. Forman1Dominique Bihan2Anna M. Puszkarska3Rakesh Rajan4David G. Reid5David A. Slatter6Lucy J. Colwell7David J. Wales8Richard W. Farndale9Melinda J. Duer10Department of Chemistry, University of CambridgeDepartment of Chemistry, University of CambridgeDepartment of Biochemistry, University of CambridgeDepartment of Chemistry, University of CambridgeDepartment of Chemistry, University of CambridgeDepartment of Chemistry, University of CambridgeInstitute of Infection and Immunity, School of Medicine, Cardiff UniversityDepartment of Chemistry, University of CambridgeDepartment of Chemistry, University of CambridgeDepartment of Biochemistry, University of CambridgeDepartment of Chemistry, University of CambridgeAbstract 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.https://doi.org/10.1038/s41598-018-31937-x13Cγ Chemical ShiftsProline RingCollagen Model PeptidesCollagen Triple HelixBackbone Dihedrals |
| spellingShingle | Wing Ying Chow Chris J. Forman Dominique Bihan Anna M. Puszkarska Rakesh Rajan David G. Reid David A. Slatter Lucy J. Colwell David J. Wales Richard W. Farndale Melinda J. Duer Proline provides site-specific flexibility for in vivo collagen Scientific Reports 13Cγ Chemical Shifts Proline Ring Collagen Model Peptides Collagen Triple Helix Backbone Dihedrals |
| title | Proline provides site-specific flexibility for in vivo collagen |
| title_full | Proline provides site-specific flexibility for in vivo collagen |
| title_fullStr | Proline provides site-specific flexibility for in vivo collagen |
| title_full_unstemmed | Proline provides site-specific flexibility for in vivo collagen |
| title_short | Proline provides site-specific flexibility for in vivo collagen |
| title_sort | proline provides site specific flexibility for in vivo collagen |
| topic | 13Cγ Chemical Shifts Proline Ring Collagen Model Peptides Collagen Triple Helix Backbone Dihedrals |
| url | https://doi.org/10.1038/s41598-018-31937-x |
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