Structural highlights
FunctionPCDGF_HUMAN Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. Publication Abstract from PubMedProtocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop and maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of the antiparallel EC1-4 homodimer of human PcdhgammaB3, a member of the gamma subfamily of clustered Pcdhs. Structure and sequence comparisons of alpha, beta, and gamma clustered Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification of loop region structure and composition in EC2 and EC3, which contains isoform-specific conservation of primarily polar residues. In contrast, the EC1/EC4 interface comprises hydrophobic interactions that provide non-selective dimerization affinity. Using sequence coevolution analysis, we found evidence for a similar antiparallel EC1-4 interaction in non-clustered Pcdh families. We thus deduce that the EC1-4 antiparallel homodimer is a general interaction strategy that evolved before the divergence of these distinct protocadherin families. Antiparallel protocadherin homodimers use distinct affinity- and specificity-mediating regions in cadherin repeats 1-4.,Nicoludis JM, Vogt BE, Green AG, Scharfe CP, Marks DS, Gaudet R Elife. 2016 Jul 29;5. pii: e18449. doi: 10.7554/eLife.18449. PMID:27472898[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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