Background: The integrin I domain undergoes a conformational change during activation. Results: The crystal structure of an activated I domain is different from the reported open and closed states. Conclusion: Our structure mimics the state where the Arg 287 -Glu 317 ion pair is just broken during the activation process. Significance: The activation mechanism of the collagen receptor integrins differs from the other integrins.

We have analyzed the structure and function of the integrin 1I 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, soluble1I C139S/E317A was a higher avidity collagen binder than 1I C139S, indicating that the double variant represents an activated form. The crystal structure of the activated variant of 1I was solved at 1.9 A res