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Publication Abstract from PubMed

Cell adhesion by classical cadherins is mediated by dimerization of their EC1 domains through the 'swapping' of N-terminal beta-strands. We use molecular simulations, measurements of binding affinities and X-ray crystallography to provide a detailed picture of the structural and energetic factors that control the adhesive dimerization of cadherins. We show that strand swapping in EC1 is driven by conformational strain in cadherin monomers that arises from the anchoring of their short N-terminal strand at one end by the conserved Trp2 and at the other by ligation to Ca(2+) ions. We also demonstrate that a conserved proline-proline motif functions to avoid the formation of an overly tight interface where affinity differences between different cadherins, crucial at the cellular level, are lost. We use these findings to design site-directed mutations that transform a monomeric EC2-EC3 domain cadherin construct into a strand-swapped dimer.

Molecular design principles underlying beta-strand swapping in the adhesive dimerization of cadherins.,Vendome J, Posy S, Jin X, Bahna F, Ahlsen G, Shapiro L, Honig B Nat Struct Mol Biol. 2011 Jun;18(6):693-700. doi: 10.1038/nsmb.2051. Epub 2011, May 15. PMID:21572446^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.