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Resolving the molecular mechanism of cadherin catch bond formation

Kristine Manibog, Hui Li, Sabyasachi Rakshit and Sanjeevi Sivasankar ()
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Kristine Manibog: Iowa State University
Hui Li: Iowa State University
Sabyasachi Rakshit: Iowa State University
Sanjeevi Sivasankar: Iowa State University

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract Classical cadherin Ca2+-dependent cell–cell adhesion proteins play key roles in embryogenesis and in maintaining tissue integrity. Cadherins mediate robust adhesion by binding in multiple conformations. One of these adhesive states, called an X-dimer, forms catch bonds that strengthen and become longer lived in the presence of mechanical force. Here we use single-molecule force-clamp spectroscopy with an atomic force microscope along with molecular dynamics and steered molecular dynamics simulations to resolve the molecular mechanisms underlying catch bond formation and the role of Ca2+ ions in this process. Our data suggest that tensile force bends the cadherin extracellular region such that they form long-lived, force-induced hydrogen bonds that lock X-dimers into tighter contact. When Ca2+ concentration is decreased, fewer de novo hydrogen bonds are formed and catch bond formation is eliminated.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4941

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DOI: 10.1038/ncomms4941

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