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Free keywords:
INTEGRIN ACTIVATION; MYOSIN-II; STRUCTURAL BASIS; TALIN; ADHESION;
CATCH; LOCALIZATION; TRANSDUCTION; FIBRONECTIN; MOLECULESScience & Technology - Other Topics; optical tweezers; ideal bond; focal adhesion; integrins; single-molecule;
Abstract:
Integrin-mediated adhesion is essential for metazoan life. Integrin binding to ligand requires an activation step prior to binding ligand that depends on direct binding of talin and kindlin to the P- integrin cytoplasmic tail and the transmission of force from the actomyosin via talin to the integrin-ligand bonds. However, the affinity of talin for integrin tails is low. It is therefore still unclear how such low-affinity bonds are reinforced to transmit forces up to 10 to 40 pN. In this study, we use single-molecule force spectroscopy by optical tweezers to investigate the mechanical stability of the talin & BULL;integrin bond in the presence and absence of kindlin. While talin and integrin alone form a weak and highly dynamic slip bond, the addition of kindlin- 2 induces a force-independent, ideal talin & BULL;integrin bond, which relies on the steric proximity of and the intervening amino acid sequences between the talin-and kindlin-binding sites in the P-integrin tail. Our findings show how kindlin cooperates with talin to enable transmission of high forces required to stabilize cell adhesion.
