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Publication Abstract from PubMed

Stochastic cell-surface expression of alpha-, beta-, and gamma-clustered protocadherins (Pcdhs) provides vertebrate neurons with single-cell identities that underlie neuronal self-recognition. Here we report crystal structures of ectodomain fragments comprising cell-cell recognition regions of mouse gamma-Pcdhs gammaA1, gammaA8, gammaB2, and gammaB7 revealing trans-homodimers, and of C-terminal ectodomain fragments from gamma-Pcdhs gammaA4 and gammaB2, which depict cis-interacting regions in monomeric form. Together these structures span the entire gamma-Pcdh ectodomain. The trans-dimer structures reveal determinants of gamma-Pcdh isoform-specific homophilic recognition. We identified and structurally mapped cis-dimerization mutations to the C-terminal ectodomain structures. Biophysical studies showed that Pcdh ectodomains from gammaB-subfamily isoforms formed cis dimers, whereas gammaA isoforms did not, but both gammaA and gammaB isoforms could interact in cis with alpha-Pcdhs. Together, these data show how interaction specificity is distributed over all domains of the gamma-Pcdh trans interface, and suggest that subfamily- or isoform-specific cis-interactions may play a role in the Pcdh-mediated neuronal self-recognition code.

gamma-Protocadherin structural diversity and functional implications.,Goodman KM, Rubinstein R, Thu CA, Mannepalli S, Bahna F, Ahlsen G, Rittenhouse C, Maniatis T, Honig B, Shapiro L Elife. 2016 Oct 26;5. pii: e20930. doi: 10.7554/eLife.20930. PMID:27782885^[1]

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