Title : Structure of an integrin with an alphaI
domain , complement receptor type 4
Abstract :
- We report the structure of an integrin with an alphaI domain , alpha(X)beta(2), the complement receptor type 4
- It was earlier expected that a fixed orientation between the alphaI domain and the beta-propeller domain in which it is inserted would be required for allosteric signal transmission
- However, the alphaI domain is highly flexible, enabling two betaI domain conformational states to couple to three alphaI domain states, and greater accessibility for ligand recognition
- Although alpha(X)beta(2) is bent similarly to integrins that lack alphaI domains , the terminal domains of the alpha- and beta-legs, calf-2 and beta-tail, are oriented differently than in alphaI-less integrins
- Linkers extending to the transmembrane domains are unstructured
- Previous mutations in the beta(2)-tail domain support the importance of extension, rather than a deadbolt, in integrin activation
- The locations of further activating mutations and antibody epitopes show the critical role of extension, and conversion from the closed to the open headpiece conformation, in integrin activation
- Differences among 10 molecules in crystal lattices provide unprecedented information on interdomain flexibility important for modelling integrin extension and activation