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Talin activates integrins by altering the topology of the ? transmembrane domain.

ABSTRACT: Talin binding to integrin ? tails increases ligand binding affinity (activation). Changes in ? transmembrane domain (TMD) topology that disrupt ?-? TMD interactions are proposed to mediate integrin activation. In this paper, we used membrane-embedded integrin ?3 TMDs bearing environmentally sensitive fluorophores at inner or outer membrane water interfaces to monitor talin-induced ?3 TMD motion in model membranes. Talin binding to the ?3 cytoplasmic domain increased amino acid side chain embedding at the inner and outer borders of the ?3 TMD, indicating altered topology of the ?3 TMD. Talin's capacity to effect this change depended on its ability to bind to both the integrin ? tail and the membrane. Introduction of a flexible hinge at the midpoint of the ?3 TMD decoupled the talin-induced change in intracellular TMD topology from the extracellular side and blocked talin-induced activation of integrin ?IIb?3. Thus, we show that talin binding to the integrin ? TMD alters the topology of the TMD, resulting in integrin activation.

PROVIDER: S-EPMC3365499 | BioStudies |

REPOSITORIES: biostudies

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