Functional analysis of the structural basis of homophilic cadherin adhesion

B. Zhu, S. Chappuis-Flament, E. Wong, I. E. Jensen, B. M. Gumbiner, Deborah E Leckband

Research output: Contribution to journalArticle

Abstract

The structures of many cell surface adhesion proteins comprise multiple tandem repeats of structurally similar domains. In many cases, the functional significance of this architecture is unknown, and there are several cases in which evidence for individual domain involvement in adhesion has been contradictory. In particular, the extracellular region of the adhesion glycoprotein cadherin consists of five tandemly arranged domains. One proposed mechanism postulated that adhesion involves only trans interactions between the outermost domains. However, subsequent investigations have generated several competing models. Here we describe direct measurements of the distance-dependent interaction potentials between cadherin mutants lacking different domains. By quantifying both the absolute distances at which opposed cadherin fragments bind and the quantized changes in the interaction potentials that result from deletions of individual domains, we demonstrate that two domains participate in homophilic cadherin binding. This finding contrasts with the current view that cadherins bind via a single, unique site on the protein surface. The potentials that result from interactions involving multiple domains generate a novel, modular binding mechanism in which opposed cadherin ectodomains can adhere in any of three antiparallel alignments.

Original languageEnglish (US)
Pages (from-to)4033-4042
Number of pages10
JournalBiophysical journal
Volume84
Issue number6
DOIs
StatePublished - Jun 1 2003

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Cadherins
Membrane Proteins
Tandem Repeat Sequences
Cell Adhesion
Glycoproteins

ASJC Scopus subject areas

  • Biophysics

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Functional analysis of the structural basis of homophilic cadherin adhesion. / Zhu, B.; Chappuis-Flament, S.; Wong, E.; Jensen, I. E.; Gumbiner, B. M.; Leckband, Deborah E.

In: Biophysical journal, Vol. 84, No. 6, 01.06.2003, p. 4033-4042.

Research output: Contribution to journalArticle

Zhu, B, Chappuis-Flament, S, Wong, E, Jensen, IE, Gumbiner, BM & Leckband, DE 2003, 'Functional analysis of the structural basis of homophilic cadherin adhesion', Biophysical journal, vol. 84, no. 6, pp. 4033-4042. https://doi.org/10.1016/S0006-3495(03)75129-7
Zhu, B. ; Chappuis-Flament, S. ; Wong, E. ; Jensen, I. E. ; Gumbiner, B. M. ; Leckband, Deborah E. / Functional analysis of the structural basis of homophilic cadherin adhesion. In: Biophysical journal. 2003 ; Vol. 84, No. 6. pp. 4033-4042.
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