Editing Integrin (section)

=== Activation ===

When released into the cell membrane, newly synthesized integrin dimers are speculated to be found in the same "bent" conformation revealed by the structural studies described above.  One school of thought claims that this bent form prevents them from interacting with their ligands, although bent forms can predominate in high-resolution EM structures of integrin bound to an ECM ligand. Therefore, at least in biochemical experiments, integrin dimers must apparently not be 'unbent' in order to prime them and allow their binding to the [[Extracellular matrix|ECM]]. In cells, the priming  is accomplished by a protein talin, which binds to the β tail of the integrin dimer and changes its conformation.<ref name="pmid15157154">{{cite journal | vauthors = Calderwood DA | title = Talin controls integrin activation | journal = Biochemical Society Transactions | volume = 32 | issue = Pt3 | pages = 434–7 | date = June 2004 | pmid = 15157154 | doi = 10.1042/BST0320434 }}</ref><ref name="pmid10497155">{{cite journal | vauthors = Calderwood DA, Zent R, Grant R, Rees DJ, Hynes RO, Ginsberg MH | title = The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 40 | pages = 28071–4 | date = October 1999 | pmid = 10497155 | doi = 10.1074/jbc.274.40.28071 | doi-access = free }}</ref> The α and β integrin chains are both class-I transmembrane proteins: they pass the plasma membrane as single transmembrane alpha-helices. Unfortunately, the helices are too long, and recent studies suggest that, for integrin gpIIbIIIa, they are tilted with respect both to one another and to the plane of the membrane. Talin binding alters the angle of tilt of the β3 chain transmembrane helix in model systems and this may reflect a stage in the process of inside-out signalling which primes integrins.<ref name="PMID20308986">{{cite journal | vauthors = Shattil SJ, Kim C, Ginsberg MH | title = The final steps of integrin activation: the end game | journal = Nature Reviews. Molecular Cell Biology | volume = 11 | issue = 4 | pages = 288–300 | date = April 2010 | pmid = 20308986 | pmc = 3929966 | doi = 10.1038/nrm2871 }}</ref> Moreover, talin proteins are able to dimerize<ref name="pmid8031639">{{cite journal | vauthors = Goldmann WH, Bremer A, Häner M, Aebi U, Isenberg G | title = Native talin is a dumbbell-shaped homodimer when it interacts with actin | journal = Journal of Structural Biology | volume = 112 | issue = 1 | pages = 3–10 | year = 1994 | pmid = 8031639 | doi = 10.1006/jsbi.1994.1002 }}</ref> and thus are thought to intervene in the clustering of integrin dimers which leads to the formation of a [[focal adhesion]]. Recently, the [[Kindlin-1]] and [[Kindlin-2]] proteins have also been found to interact with integrin and activate it.<ref name="pmid19240021">{{cite journal | vauthors = Harburger DS, Bouaouina M, Calderwood DA | title = Kindlin-1 and -2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects | journal = The Journal of Biological Chemistry | volume = 284 | issue = 17 | pages = 11485–97 | date = April 2009 | pmid = 19240021 | pmc = 2670154 | doi = 10.1074/jbc.M809233200 | doi-access = free }}</ref>