3qrb
From Proteopedia
crystal structure of E-cadherin EC1-2 P5A P6A
Structural highlights
Function[CADH1_MOUSE] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7 (By similarity). E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production (By similarity). Publication Abstract from PubMedCell 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. See AlsoReferences
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