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Unique charge-dependent constraint on collagen recognition by integrin α10β1

The collagen-binding integrins recognise collagen through their inserted (I) domain, where co-ordination of a Mg(2 +) ion in the metal ion-dependent site is reorganised by ligation by a collagen glutamate residue found in specific collagen hexapeptide motifs. Here we show that GROGER, found in the N...

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Autores principales: Hamaia, Samir W., Luff, Daisy, Hunter, Emma J., Malcor, Jean-Daniel, Bihan, Dominique, Gullberg, Donald, Farndale, Richard W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380659/
https://www.ncbi.nlm.nih.gov/pubmed/27569273
http://dx.doi.org/10.1016/j.matbio.2016.08.010
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author Hamaia, Samir W.
Luff, Daisy
Hunter, Emma J.
Malcor, Jean-Daniel
Bihan, Dominique
Gullberg, Donald
Farndale, Richard W.
author_facet Hamaia, Samir W.
Luff, Daisy
Hunter, Emma J.
Malcor, Jean-Daniel
Bihan, Dominique
Gullberg, Donald
Farndale, Richard W.
author_sort Hamaia, Samir W.
collection PubMed
description The collagen-binding integrins recognise collagen through their inserted (I) domain, where co-ordination of a Mg(2 +) ion in the metal ion-dependent site is reorganised by ligation by a collagen glutamate residue found in specific collagen hexapeptide motifs. Here we show that GROGER, found in the N-terminal domain of collagens I and III, is only weakly recognised by α10β1, an important collagen receptor on chondrocytes, contrasting with the other collagen-binding integrins. Alignment of I domain sequence and molecular modelling revealed a clash between a unique arginine residue (R215) in α10β1 and the positively-charged GROGER. Replacement of R215 with glutamine restored binding. Substituting arginine at the equivalent locus (Q214) in integrins α1 and α2 I domains impaired their binding to GROGER. Collagen II, abundant in cartilage, lacks GROGER. GRSGET is uniquely expressed in the C-terminus of collagen II, but this motif is similarly not recognised by α10β1. These data suggest an evolutionary imperative to maintain accessibility of the terminal domains of collagen II in tissues such as cartilage, perhaps during endochondral ossification, where α10β1 is the main collagen-binding integrin.
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spelling pubmed-53806592017-05-01 Unique charge-dependent constraint on collagen recognition by integrin α10β1 Hamaia, Samir W. Luff, Daisy Hunter, Emma J. Malcor, Jean-Daniel Bihan, Dominique Gullberg, Donald Farndale, Richard W. Matrix Biol Article The collagen-binding integrins recognise collagen through their inserted (I) domain, where co-ordination of a Mg(2 +) ion in the metal ion-dependent site is reorganised by ligation by a collagen glutamate residue found in specific collagen hexapeptide motifs. Here we show that GROGER, found in the N-terminal domain of collagens I and III, is only weakly recognised by α10β1, an important collagen receptor on chondrocytes, contrasting with the other collagen-binding integrins. Alignment of I domain sequence and molecular modelling revealed a clash between a unique arginine residue (R215) in α10β1 and the positively-charged GROGER. Replacement of R215 with glutamine restored binding. Substituting arginine at the equivalent locus (Q214) in integrins α1 and α2 I domains impaired their binding to GROGER. Collagen II, abundant in cartilage, lacks GROGER. GRSGET is uniquely expressed in the C-terminus of collagen II, but this motif is similarly not recognised by α10β1. These data suggest an evolutionary imperative to maintain accessibility of the terminal domains of collagen II in tissues such as cartilage, perhaps during endochondral ossification, where α10β1 is the main collagen-binding integrin. Elsevier 2017-05 /pmc/articles/PMC5380659/ /pubmed/27569273 http://dx.doi.org/10.1016/j.matbio.2016.08.010 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hamaia, Samir W.
Luff, Daisy
Hunter, Emma J.
Malcor, Jean-Daniel
Bihan, Dominique
Gullberg, Donald
Farndale, Richard W.
Unique charge-dependent constraint on collagen recognition by integrin α10β1
title Unique charge-dependent constraint on collagen recognition by integrin α10β1
title_full Unique charge-dependent constraint on collagen recognition by integrin α10β1
title_fullStr Unique charge-dependent constraint on collagen recognition by integrin α10β1
title_full_unstemmed Unique charge-dependent constraint on collagen recognition by integrin α10β1
title_short Unique charge-dependent constraint on collagen recognition by integrin α10β1
title_sort unique charge-dependent constraint on collagen recognition by integrin α10β1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380659/
https://www.ncbi.nlm.nih.gov/pubmed/27569273
http://dx.doi.org/10.1016/j.matbio.2016.08.010
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