Protocadherin cis-dimer architecture and recognition unit diversity

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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.

Original languageEnglish
Pages (from-to)E9829-E9837
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number46
StatePublished - 14 Nov 2017
Externally publishedYes


FundersFunder number
Department of Systems Biology at Columbia University
NIH instrumentationS10OD021764, S10OD012351
National Science FoundationMCB-1412472, R01GM107571
National Institutes of HealthP41GM103403
National Institute of Mental HealthR01MH114817


    • Clustered protocadherin
    • Crystal structure
    • Neuronal self-avoidance
    • Protein–protein interaction
    • Self-recognition


    Dive into the research topics of 'Protocadherin cis-dimer architecture and recognition unit diversity'. Together they form a unique fingerprint.

    Cite this