5dzx
Protocadherin beta 6 extracellular cadherin domains 1-4
Structural highlights
FunctionPCDB6_MOUSE Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination (PubMed:27161523). Thereby, it is involved in the establishment and maintenance of specific neuronal connections in the brain (PubMed:27161523).[1] Publication Abstract from PubMedClustered protocadherin proteins (alpha-, beta-, and gamma-Pcdhs) provide a high level of cell-surface diversity to individual vertebrate neurons, engaging in highly specific homophilic interactions to mediate important roles in mammalian neural circuit development. How Pcdhs bind homophilically through their extracellular cadherin (EC) domains among dozens of highly similar isoforms has not been determined. Here, we report crystal structures for extracellular regions from four mouse Pcdh isoforms (alpha4, alpha7, beta6, and beta8), revealing a canonical head-to-tail interaction mode for homophilic trans dimers comprising primary intermolecular EC1:EC4 and EC2:EC3 interactions. A subset of trans interface residues exhibit isoform-specific conservation, suggesting roles in recognition specificity. Mutation of these residues, along with trans-interacting partner residues, altered the specificities of Pcdh interactions. Together, these data show how sequence variation among Pcdh isoforms encodes their diverse strict homophilic recognition specificities, which are required for their key roles in neural circuit assembly. Structural Basis of Diverse Homophilic Recognition by Clustered alpha- and beta-Protocadherins.,Goodman KM, Rubinstein R, Thu CA, Bahna F, Mannepalli S, Ahlsen G, Rittenhouse C, Maniatis T, Honig B, Shapiro L Neuron. 2016 May 18;90(4):709-23. doi: 10.1016/j.neuron.2016.04.004. Epub 2016, May 5. PMID:27161523[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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