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Nat Commun. 2014 Jun 2;5:3941. doi: 10.1038/ncomms4941.

Resolving the molecular mechanism of cadherin catch bond formation.

Author information

1
1] Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011, USA [2] Ames Laboratory, United States Department of Energy, Ames, Iowa 50011, USA.
2
1] Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011, USA [2] Ames Laboratory, United States Department of Energy, Ames, Iowa 50011, USA [3].

Abstract

Classical cadherin Ca(2+)-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 Ca(2+) 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 Ca(2+) concentration is decreased, fewer de novo hydrogen bonds are formed and catch bond formation is eliminated.

PMID:
24887573
DOI:
10.1038/ncomms4941
[Indexed for MEDLINE]

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