title: Two-step adhesive binding by classical cadherins.
abstract: Crystal structures of classical cadherins have revealed two dimeric configurations. In the first, N-terminal beta-strands of EC1 domains 'swap' between partner molecules. The second configuration (the 'X dimer'), also observed for T-cadherin, is mediated by residues near the EC1-EC2 calcium binding sites, and N-terminal beta-strands of partner EC1 domains, though held adjacent, do not swap. Here we show that strand-swapping mutants of type I and II classical cadherins form X dimers. Mutant cadherins impaired for X-dimer formation show no binding in short-time frame surface plasmon resonance assays, but in long-time frame experiments, they have homophilic binding affinities close to that of wild type. Further experiments show that exchange between monomers and dimers is slowed in these mutants. These results reconcile apparently disparate results from prior structural studies and suggest that X dimers are binding intermediates that facilitate the formation of strand-swapped dimers.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Harrison
authors.forename: Fabiana
authors.initials: F
authors.lastname: Bahna
authors.forename: Phini S
authors.initials: PS
authors.lastname: Katsamba
authors.forename: Xiangshu
authors.initials: X
authors.lastname: Jin
authors.forename: Julia
authors.initials: J
authors.lastname: Brasch
authors.forename: Jeremie
authors.initials: J
authors.lastname: Vendome
authors.forename: Goran
authors.initials: G
authors.lastname: Ahlsen
authors.forename: Kilpatrick J
authors.initials: KJ
authors.lastname: Carroll
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Price
authors.forename: Barry
authors.initials: B
authors.lastname: Honig
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D009154:Mutation; D011485:Protein Binding / Q000502:physiology; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology; D017433:Protein Structure, Secondary; D020349:Surface Plasmon Resonance; D014461:Ultracentrifugation
chemical_list: D015820:Cadherins