Kindlin stabilizes the talin·integrin bond under mechanical load by generating an ideal bond

Author:

Bodescu Mihai Adrian1,Aretz Jonas2ORCID,Grison Marco1,Rief Matthias1,Fässler Reinhard2

Affiliation:

1. Center for Protein Assemblies and TUM School of Natural Sciences, Department of Bioscience, Chair of Molecular Biophysics, Technical University of Munich, Garching 85748, Germany

2. Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried 82152, Germany

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 β-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•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•integrin bond, which relies on the steric proximity of and the intervening amino acid sequences between the talin- and kindlin-binding sites in the β-integrin tail. Our findings show how kindlin cooperates with talin to enable transmission of high forces required to stabilize cell adhesion.

Funder

EC | European Research Council

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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