An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens.
The GFOGER motif in collagens (O denotes hydroxyproline) represents a high-affinity binding site for all collagen-binding integrins. Other GxOGER motifs require integrin activation for maximal binding. The E318W mutant of the integrin α2β1 I domain displays a relaxed collagen specificity, typical of...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0069833 |
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| author | Federico Carafoli Samir W Hamaia Dominique Bihan Erhard Hohenester Richard W Farndale |
| author_facet | Federico Carafoli Samir W Hamaia Dominique Bihan Erhard Hohenester Richard W Farndale |
| author_sort | Federico Carafoli |
| collection | DOAJ |
| description | The GFOGER motif in collagens (O denotes hydroxyproline) represents a high-affinity binding site for all collagen-binding integrins. Other GxOGER motifs require integrin activation for maximal binding. The E318W mutant of the integrin α2β1 I domain displays a relaxed collagen specificity, typical of an active state. E318W binds more strongly than the wild-type α2 I domain to GMOGER, and forms a 2:1 complex with a homotrimeric, collagen-like, GFOGER peptide. Crystal structure analysis of this complex reveals two E318W I domains, A and B, bound to a single triple helix. The E318W I domains are virtually identical to the collagen-bound wild-type I domain, suggesting that the E318W mutation activates the I domain by destabilising the unligated conformation. E318W I domain A interacts with two collagen chains similarly to wild-type I domain (high-affinity mode). E318W I domain B makes favourable interactions with only one collagen chain (low-affinity mode). This observation suggests that single GxOGER motifs in the heterotrimeric collagens V and IX may support binding of activated integrins. |
| format | Article |
| id | doaj-art-9d1d9f11f659498bb0ecce99ea3115f0 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9d1d9f11f659498bb0ecce99ea3115f02025-08-20T02:35:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6983310.1371/journal.pone.0069833An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens.Federico CarafoliSamir W HamaiaDominique BihanErhard HohenesterRichard W FarndaleThe GFOGER motif in collagens (O denotes hydroxyproline) represents a high-affinity binding site for all collagen-binding integrins. Other GxOGER motifs require integrin activation for maximal binding. The E318W mutant of the integrin α2β1 I domain displays a relaxed collagen specificity, typical of an active state. E318W binds more strongly than the wild-type α2 I domain to GMOGER, and forms a 2:1 complex with a homotrimeric, collagen-like, GFOGER peptide. Crystal structure analysis of this complex reveals two E318W I domains, A and B, bound to a single triple helix. The E318W I domains are virtually identical to the collagen-bound wild-type I domain, suggesting that the E318W mutation activates the I domain by destabilising the unligated conformation. E318W I domain A interacts with two collagen chains similarly to wild-type I domain (high-affinity mode). E318W I domain B makes favourable interactions with only one collagen chain (low-affinity mode). This observation suggests that single GxOGER motifs in the heterotrimeric collagens V and IX may support binding of activated integrins.https://doi.org/10.1371/journal.pone.0069833 |
| spellingShingle | Federico Carafoli Samir W Hamaia Dominique Bihan Erhard Hohenester Richard W Farndale An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens. PLoS ONE |
| title | An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens. |
| title_full | An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens. |
| title_fullStr | An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens. |
| title_full_unstemmed | An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens. |
| title_short | An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens. |
| title_sort | activating mutation reveals a second binding mode of the integrin α2 i domain to the gfoger motif in collagens |
| url | https://doi.org/10.1371/journal.pone.0069833 |
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