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PDBsum entry 5ypr
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Protein binding
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PDB id
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5ypr
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References listed in PDB file
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Key reference
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Title
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Synaptic targeting and function of sapaps mediated by phosphorylation-Dependent binding to psd-95 maguks.
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Authors
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J.Zhu,
Q.Zhou,
Y.Shang,
H.Li,
M.Peng,
X.Ke,
Z.Weng,
R.Zhang,
X.Huang,
S.S.C.Li,
G.Feng,
Y.Lu,
M.Zhang.
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Ref.
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Cell Rep, 2017,
21,
3781-3793.
[DOI no: ]
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PubMed id
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Abstract
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The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating
the formation and plasticity of the post-synaptic densities (PSDs). We
previously demonstrated that the exquisitely specific SAPAP/Shank interaction is
critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here,
we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and
SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat
sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in
complex with a phosphor-SAPAP repeat peptide, together with biochemical studies,
reveals the molecular mechanism underlying the phosphorylation-dependent
PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95
mutation found in patients with intellectual disabilities. Guided by the
structural data, we developed potent non-phosphorylated GK inhibitory peptides
capable of blocking the PSD-95/SAPAP interaction and interfering with
PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are
genetically encodable for investigating the functions of the PSD-95/SAPAP
interaction in vivo.
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