Talin activates integrins by altering the topology of the β transmembrane domain

Chungho Kim, Feng Ye, Xiaohui Hu, Mark H. Ginsberg

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Talin binding to integrin β tails increases ligand binding affinity (activation). Changes in β transmembrane domain (TMD) topology that disrupt α-β TMD interactions are proposed to mediate integrin activation. In this paper, we used membrane-embedded integrin β3 TMDs bearing environmentally sensitive fluorophores at inner or outer membrane water interfaces to monitor talin-induced β3 TMD motion in model membranes. Talin binding to the β3 cytoplasmic domain increased amino acid side chain embedding at the inner and outer borders of the β3 TMD, indicating altered topology of the β3 TMD. Talin's capacity to effect this change depended on its ability to bind to both the integrin β tail and the membrane. Introduction of a flexible hinge at the midpoint of the β3 TMD decoupled the talin-induced change in intracellular TMD topology from the extracellular side and blocked talin-induced activation of integrin αIIbβ3. Thus, we show that talin binding to the integrin β TMD alters the topology of the TMD, resulting in integrin activation.

Original languageEnglish
Pages (from-to)605-611
Number of pages7
JournalJournal of Cell Biology
Volume197
Issue number5
DOIs
Publication statusPublished - 2012 May

ASJC Scopus subject areas

  • Cell Biology

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