| Literature DB >> 29087338 |
Kerry M Goodman1,2, Rotem Rubinstein3, Hanbin Dan3, Fabiana Bahna2,4, Seetha Mannepalli1,2, Göran Ahlsén2,3,4, Chan Aye Thu1, Rosemary V Sampogna5, Tom Maniatis6,2, Barry Honig6,2,3,4,5, Lawrence Shapiro6,2.
Abstract
Clustered protocadherins (Pcdhs) mediate numerous neural patterning functions, including neuronal self-recognition and non-self-discrimination to direct self-avoidance among vertebrate neurons. Individual neurons stochastically express a subset of Pcdh isoforms, which assemble to form a stochastic repertoire of cis-dimers. We describe the structure of a PcdhγB7 cis-homodimer, which includes the membrane-proximal extracellular cadherin domains EC5 and EC6. The structure is asymmetric with one molecule contributing interface surface from both EC5 and EC6, and the other only from EC6. Structural and sequence analyses suggest that all Pcdh isoforms will dimerize through this interface. Site-directed mutants at this interface interfere with both Pcdh cis-dimerization and cell surface transport. The structure explains the known restrictions of cis-interactions of some Pcdh isoforms, including α-Pcdhs, which cannot form homodimers. The asymmetry of the interface approximately doubles the size of the recognition repertoire, and restrictions on cis-interactions among Pcdh isoforms define the limits of the Pcdh recognition unit repertoire.Entities:
Keywords: clustered protocadherin; crystal structure; neuronal self-avoidance; protein–protein interaction; self-recognition
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Year: 2017 PMID： 29087338 PMCID： PMC5699079 DOI： 10.1073/pnas.1713449114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205