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PDBsum entry 4zpq
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Cell adhesion
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PDB id
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4zpq
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References listed in PDB file
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Key reference
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Title
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Molecular logic of neuronal self-Recognition through protocadherin domain interactions.
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Authors
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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.
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Ref.
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Cell, 2015,
163,
629-642.
[DOI no: ]
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PubMed id
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Abstract
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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.
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