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PDBsum entry 4pbw
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Signaling protein
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PDB id
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4pbw
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References listed in PDB file
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Key reference
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Title
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Structural basis for extracellular cis and trans rptpσ signal competition in synaptogenesis.
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Authors
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C.H.Coles,
N.Mitakidis,
P.Zhang,
J.Elegheert,
W.Lu,
A.W.Stoker,
T.Nakagawa,
A.M.Craig,
E.Y.Jones,
A.R.Aricescu.
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Ref.
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Nat Commun, 2014,
5,
5209.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Receptor protein tyrosine phosphatase sigma (RPTPσ) regulates neuronal
extension and acts as a presynaptic nexus for multiple protein and proteoglycan
interactions during synaptogenesis. Unknown mechanisms govern the shift in
RPTPσ function, from outgrowth promotion to synaptic organization. Here, we
report crystallographic, electron microscopic and small-angle X-ray scattering
analyses, which reveal sufficient inter-domain flexibility in the RPTPσ
extracellular region for interaction with both cis (same cell) and trans
(opposite cell) ligands. Crystal structures of RPTPσ bound to its postsynaptic
ligand TrkC detail an interaction surface partially overlapping the
glycosaminoglycan-binding site. Accordingly, heparan sulphate and heparin
oligomers compete with TrkC for RPTPσ binding in vitro and disrupt
TrkC-dependent synaptic differentiation in neuronal co-culture assays. We
propose that transient RPTPσ ectodomain emergence from the presynaptic
proteoglycan layer allows capture by TrkC to form a trans-synaptic complex, the
consequent reduction in RPTPσ flexibility potentiating interactions with
additional ligands to orchestrate excitatory synapse formation.
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