PDBsum entry 4zps

Cell adhesion

PDB id: 4zps

Contents

Protein chain

313 a.a.

Ligands

MAN ×2

Metals

_CA ×7

Waters ×20

PDB id:

4zps

Name:

Cell adhesion

Title:

Crystal structure of protocadherin gamma a8 ec1-3

Structure:

Mcg133388, isoform cra_m. Chain: a. Fragment: unp residues 30-342. Synonym: protein pcdhga8,protocadherin gamma a8,protocadherin gamma subfamily a,8. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: pcdhga8, mcg_133388. Expressed in: homo sapiens. Expression_system_taxid: 9606

Resolution:

2.90Å R-factor: 0.266 R-free: 0.287

Authors:

K.M.Goodman,S.Mannepalli,L.Shapiro

Key ref:

R.Rubinstein et al. (2015). Molecular logic of neuronal self-recognition through protocadherin domain interactions. Cell, 163, 629-642. PubMed id: 26478182 DOI: 10.1016/j.cell.2015.09.026

Date:

08-May-15 Release date: 28-Oct-15

Protein chain

Q91XY0  (Q91XY0_MOUSE) -  Protocadherin gamma A8 from Mus musculus

Seq: 932 a.a.

Struc: 313 a.a.

DOI no: 10.1016/j.cell.2015.09.026

Cell 163:629-642 (2015)

PubMed id: 26478182

Molecular logic of neuronal self-recognition through protocadherin domain interactions.

R.Rubinstein, C.A.Thu, K.M.Goodman, H.N.Wolcott, F.Bahna, S.Mannepalli, G.Ahlsen, M.Chevee, A.Halim, H.Clausen, T.Maniatis, L.Shapiro, B.Honig.

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.