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Title: Resolving the molecular mechanism of cadherin catch bond formation

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
 [1] ;  [2] ;  [2] ;  [1]
  1. Iowa State University
  2. Ames Laboratory
Publication Date:
OSTI Identifier:
Report Number(s):
IS-J 8391
Journal ID: ISSN 2041-1723
DOE Contract Number:
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature Communications; Journal Volume: 5
Research Org:
Ames Laboratory (AMES), Ames, IA (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States