Two-step Adhesive Binding by Classical Cadherins

Journal Article · Fri Jan 01 04:00:00 EST 2010 · Nature Structural and Molecular Biology

DOI:https://doi.org/10.1038/nsmb.1784· OSTI ID:1019891

Harrison, O; Bahna, F; Katsamba, P; Jin, X; Brasch, J; Carroll, K; Price, S; Honig, B; Shapiro, L

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1019891
• Report Number(s): BNL--95737-2011-JA
• Journal Information: Nature Structural and Molecular Biology, Journal Name: Nature Structural and Molecular Biology Journal Issue: 3 Vol. 17; ISSN 1545-9993
• Country of Publication: United States
• Language: English

Related Subjects

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS
ADHESIVES
CALCIUM
CONFIGURATION
CRYSTAL STRUCTURE
DIMERS
MONOMERS
MUTANTS
PLASMONS
RESIDUES
RESONANCE
national synchrotron light source