4ZPN

Crystal Structure of Protocadherin Gamma C5 EC1-3 with extended N-terminus

Summary for 4ZPN

• Entry DOI: 10.2210/pdb4zpn/pdb
• Related: 4ZPL 4ZPM 4ZPO 4ZPP 4ZPQ 4ZPS
• Descriptor: MCG133388, isoform CRA_f, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: cell adhesion
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 73714.50

Authors

Goodman, K.M.,Wolcott, H.N.,Bahna, F.,Shapiro, L. (deposition date: 2015-05-08, release date: 2015-10-28, Last modification date: 2024-10-23)

Primary citation

Rubinstein, R.,Thu, C.A.,Goodman, K.M.,Wolcott, H.N.,Bahna, F.,Mannepalli, S.,Ahlsen, G.,Chevee, M.,Halim, A.,Clausen, H.,Maniatis, T.,Shapiro, L.,Honig, B.
Molecular Logic of Neuronal Self-Recognition through Protocadherin Domain Interactions.
Cell, 163:629-642, 2015

PubMed Abstract: Self-avoidance, a process preventing interactions of axons and dendrites from the same neuron during development, is mediated in vertebrates through the stochastic single-neuron expression of clustered protocadherin protein isoforms. Extracellular cadherin (EC) domains mediate isoform-specific homophilic binding between cells, conferring cell recognition through a poorly understood mechanism. Here, we report crystal structures for the EC1-EC3 domain regions from four protocadherin isoforms representing the α, β, and γ subfamilies. All are rod shaped and monomeric in solution. Biophysical measurements, cell aggregation assays, and computational docking reveal that trans binding between cells depends on the EC1-EC4 domains, which interact in an antiparallel orientation. We also show that the EC6 domains are required for the formation of cis-dimers. Overall, our results are consistent with a model in which protocadherin cis-dimers engage in a head-to-tail interaction between EC1-EC4 domains from apposed cell surfaces, possibly forming a zipper-like protein assembly, and thus providing a size-dependent self-recognition mechanism.

PubMed: 26478182
DOI: 10.1016/j.cell.2015.09.026

Experimental method

X-RAY DIFFRACTION (3.3 Å)