γ-Protocadherin structural diversity and functional implications
Stochastic cell-surface expression of α-, β-, and γ-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 γ-Pcdhs γA1, γA8, γB2, and γB7 revealingtrans-homodimers, and of C-terminal ectodomain fragments from γ-Pcdhs γA4 and γB2, which depictcis-interacting regions in monomeric form. Together these structures span the entire γ-Pcdh ectodomain. Thetrans-dimer structures reveal determinants of γ-Pcdh isoform-specific homophilic recognition. We identified and structurally mappedcis-dimerization mutations to the C-terminal ectodomain structures. Biophysical studies showed that Pcdh ectodomains from γB-subfamily isoforms formedcisdimers, whereas γA isoforms did not, but both γA and γB isoforms could interact inciswith α-Pcdhs. Together, these data show how interaction specificity is distributed over all domains of the γ-Pcdhtransinterface, and suggest that subfamily- or isoform-specificcis-interactions may play a role in the Pcdh-mediated neuronal self-recognition code.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- NSFNIHHHMI
- OSTI ID:
- 1339750
- Journal Information:
- eLife, Vol. 5, Issue 10, 2016; ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- ENGLISH
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