4nqq

Crystal structure of mouse P-cadherin extracellular domains EC1-EC2

spinqualitylabelsall models 4nqq, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nqq is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, CU Resources: FirstGlance, OCA, RCSB, PDBsum Function [CADH3_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. Publication Abstract from PubMed Type I cadherin cell-adhesion proteins are similar in sequence and structure and yet are different enough to mediate highly specific cell-cell recognition phenomena. It has previously been shown that small differences in the homophilic and heterophilic binding affinities of different type I family members can account for the differential cell-sorting behavior. Here we use a combination of X-ray crystallography, analytical ultracentrifugation, surface plasmon resonance and double electron-electron resonance (DEER) electron paramagnetic resonance spectroscopy to identify the molecular determinants of type I cadherin dimerization affinities. Small changes in sequence are found to produce subtle structural and dynamical changes that impact relative affinities, in part via electrostatic and hydrophobic interactions, and in part through entropic effects because of increased conformational heterogeneity in the bound states as revealed by DEER distance mapping in the dimers. These findings highlight the remarkable ability of evolution to exploit a wide range of molecular properties to produce closely related members of the same protein family that have affinity differences finely tuned to mediate their biological roles. Structural and energetic determinants of adhesive binding specificity in type I cadherins.,Vendome J, Felsovalyi K, Song H, Yang Z, Jin X, Brasch J, Harrison OJ, Ahlsen G, Bahna F, Kaczynska A, Katsamba PS, Edmond D, Hubbell WL, Shapiro L, Honig B Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):E4175-84. doi:, 10.1073/pnas.1416737111. Epub 2014 Sep 24. PMID:25253890 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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