ArticleThe Journal of biological chemistry2011
Structure of collagen receptor integrin α(1)I domain carrying the activating mutation E317A.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Opticin Ameliorates Hypoxia-Induced Retinal Angiogenesis by Suppression of Integrin α2-I Domain-Collagen Complex Formation and RhoA/ROCK1 Signaling.Investigative ophthalmology & visual science · 2022Article
- Magnesium Activates Microsecond Dynamics to Regulate Integrin-Collagen Recognition.Structure (London, England : 1993) · 2018Article
- Proline hydroxylation in collagen supports integrin binding by two distinct mechanisms.The Journal of biological chemistry · 2018Article
- Salt-bridge modulates differential calcium-mediated ligand binding to integrin α1- and α2-I domains.Scientific reports · 2018Article
- Intrinsic local destabilization of the C-terminus predisposes integrin α1 I domain to a conformational switch induced by collagen binding.Protein science : a publication of the Protein Society · 2016Article
- Early chordate origin of the vertebrate integrin αI domains.PloS one · 2014Article
- The structure of integrin α1I domain in complex with a collagen-mimetic peptide.The Journal of biological chemistry · 2013Article
- An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens.PloS one · 2013Article
- Enhancing integrin α1 inserted (I) domain affinity to ligand potentiates integrin α1β1-mediated down-regulation of collagen synthesis.The Journal of biological chemistry · 2012Article
- Dynamic structural changes are observed upon collagen and metal ion binding to the integrin α1 I domain.The Journal of biological chemistry · 2012Article
- Mapping of potent and specific binding motifs, GLOGEN and GVOGEA, for integrin α1β1 using collagen toolkits II and III.The Journal of biological chemistry · 2012Article
- Crystal structure of α5β1 integrin ectodomain: atomic details of the fibronectin receptor.The Journal of cell biology · 2012Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have analyzed the structure and function of the integrin α(1)I domain harboring a gain-of-function mutation E317A. To promote protein crystallization, a double variant with an additional C139S mutation was used. In cell adhesion assays, the E317A mutation promoted binding to collagen. Similarly, the double mutation C139S/E317A increased adhesion compared with C139S alone. Furthermore, soluble α(1)I C139S/E317A was a higher avidity collagen binder than α(1)I C139S, indicating that the double variant represents an activated form. The crystal structure of the activated variant of α(1)I was solved at 1.9 Å resolution. The E317A mutation results in the unwinding of the αC helix, but the metal ion has moved toward loop 1, instead of loop 2 in the open α(2)I. Furthermore, unlike in the closed αI domains, the metal ion is pentacoordinated and, thus, prepared for ligand binding. Helix 7, which has moved downward in the open α(2)I structure, has not changed its position in the activated α(1)I variant. During the integrin activation, Glu(335) on helix 7 binds to the metal ion at the metal ion-dependent adhesion site (MIDAS) of the β(1) subunit. Interestingly, in our cell adhesion assays E317A could activate collagen binding even after mutating Glu(335). This indicates that the stabilization of helix 7 into its downward position is not required if the α(1) MIDAS is already open. To conclude, the activated α(1)I domain represents a novel conformation of the αI domain, mimicking the structural state where the Arg(287)-Glu(317) ion pair has just broken during the integrin activation.
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