Structural basis for the autoinhibition of talin in regulating integrin activation (Mol Cell, 2008, 31:124-133)

報告日期: 2008/12/09
報告時間: 17:05/17:55
報告學生: 張耀宗
講評老師: 王淑鶯

Structural Basis for the Autoinhibition of Talin in Regulating Integrin Activation

Molecular Cell 31, 124–133, July 11, 2008



Commentator: 淑鶯 老師

Date:12/9/2008 pm5:05-5:55




Integrins are essential receptors for the development and functioning of multicellular organisms because they mediate cell migration, and regulate cell proliferation, apoptosis. Control of integrin affinity (integrin activation) is essential for normal cell adhesion, migration, and assembly of an extracellular matrix. Recent results indicate that the binding of talin, a major actin-binding protein, to integrin beta tails represents a final common step in integrin activation pathways. Talin is a high molecular weight protein containing an N-terminal head (1–433, talin-H, 50 kDa) and a C-terminal rod region (434–2541, talin-R, 220 kDa).The major integrin-binding site lies within the talin FERM (four-point-one, ezrin, radixin, moesin) domain of talin-H, and binding occurs via a variant of the classical PTB domain (phosphotyrosine-binding domain)-NPxY interaction. It is well-established that talin-H can activate integrins, and it is presumed that this activity is blunted in full-length talin. Goksoy et al. show that a middle segment of talin-R can interacts with talin-FERM and competes with integrin β CT for binding to talin-PTB by performing NMR-based structural analyses.

And show that talin-R has the similar integrin membrane-proximal β CT-binding site on talin-PTB that is key for controlling the activation of integrins. They also show that the M319A mutation on talin-PTB, which does not affect talin-H/integrin interaction but disrupts the talin-H/talin-R interaction, leads to the opened conformation of full-length talin. And this finding corresponds with the Phosphatidylinositol 4,5-bisphosphate (PIP2), a known talin activator, disrupts the inhibitory talin-PTB/talin-R interaction. This report defines a structural mechanism of the talin autoinhibition and suggests how it regulates the activation of integrin.



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