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Molecular determinants of cadherin ideal bond formation: Conformation-dependent unbinding on a multidimensional landscape

TitleMolecular determinants of cadherin ideal bond formation: Conformation-dependent unbinding on a multidimensional landscape
Publication TypeJournal Article
Year of Publication2016
AuthorsManibog, K, Sankar, K, Kim, SA, Zhang, YX, Jernigan, RL, Sivasankar, S
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
PaginationE5711-E5720
Date Published09
Type of ArticleArticle
ISBN Number0027-8424
Accession NumberWOS:000383954700004
Keywordsadherens, Adhesion, adhesive binding, AFM, cell, cell-adhesion, crystal-structure, i cadherins, junctions, mechanism, mechanobiology, mediated adhesion, principal component analysis, simulations, single-molecule biophysics, single-parameter, structural basis, Technology - Other Topics
Abstract

n these predictions, we engineer cadherin mutants that promote or inhibit ideal bond formation and measure their force-dependent kinetics using single-molecule force-clamp measurements with an atomic force microscope. Our data establish that cadherins adopt an intermediate conformation as they shuttle between X-dimers and strandswap dimers; pulling on this conformation induces a torsional motion perpendicular to the pulling direction that unbinds the proteins and forms force-independent ideal bonds. Torsional motion is blocked when cadherins associate laterally in a cis orientation, suggesting that ideal bonds may play a role in mechanically regulating cadherin clustering on cell surfaces.

DOI10.1073/pnas.1604012113
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Not AL

Alternate JournalProc. Natl. Acad. Sci. U. S. A.