Protocadherin cis-dimer architecture and recognition unit diversity

Goodman, Kerry M.; Rubinstein, Rotem; Dan, Hanbin; Bahna, Fabiana; Mannepalli, Seetha; Ahlsén, Göran; Aye Thu, Chan; Sampogna, Rosemary V.; Maniatis, Tom; Honig, Barry; Shapiro, Lawrence

doi:10.1073/pnas.1713449114

Title: Protocadherin cis-dimer architecture and recognition unit diversity

Journal Article · Mon Oct 30 00:00:00 EDT 2017 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1713449114· OSTI ID:1430316

Goodman, Kerry M. ^[1]; Rubinstein, Rotem ^[1]; Dan, Hanbin ^[1]; Bahna, Fabiana ^[1]; Mannepalli, Seetha ^[1]; Ahlsén, Göran ^[1]; Aye Thu, Chan ^[1]; Sampogna, Rosemary V. ^[1]; Maniatis, Tom ^[1]; Honig, Barry ^[1]; Shapiro, Lawrence ^[1]

Columbia Univ., New York, NY (United States)

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 ofcis-dimers. We describe herein the structure of a PcdhγB7cis-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 Pcdhcis-dimerization and cell surface transport. The structure explains the known restrictions ofcis-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 oncis-interactions among Pcdh isoforms define the limits of the Pcdh recognition unit repertoire.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); National Science Foundation (NSF)

Grant/Contract Number:: P41GM103403; MCB-1412472; R01GM107571; R01MH114817; S10OD012351; S10OD021764

OSTI ID:: 1430316

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, Issue 46; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 40 works

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
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crystal structure
protein–protein interaction
neuronal self-avoidance
self-recognition

Title: Protocadherin cis-dimer architecture and recognition unit diversity

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