PDBsum entry 5ypr

Protein binding

PDB id: 5ypr

Contents

Protein chains

267 a.a.

16 a.a.

Waters ×42

PDB id:

5ypr

Name:

Protein binding

Title:

Crystal structure of psd-95 sh3-gk domain in complex with a synthesized inhibitor

Structure:

Disks large homolog 4. Chain: a. Synonym: postsynaptic density protein 95,psd-95,synapse-associated protein 90,sap90. Engineered: yes. Synthesized gk inhibitor. Chain: b. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: dlg4, dlgh4, psd95. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Resolution:

2.35Å R-factor: 0.224 R-free: 0.264

Authors:

J.Zhu,Q.Zhou,Y.Shang,Z.Weng,R.Zhu,M.Zhang

Key ref:

J.Zhu et al. (2017). Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs. Cell Rep, 21, 3781-3793. PubMed id: 29281827 DOI: 10.1016/j.celrep.2017.11.107

Date:

02-Nov-17 Release date: 14-Mar-18

Protein chain

P31016  (DLG4_RAT) -  Disks large homolog 4 from Rattus norvegicus

Seq: 724 a.a.

Struc: 267 a.a.

Protein chain

No UniProt id for this chain

Struc: 16 a.a.

DOI no: 10.1016/j.celrep.2017.11.107

Cell Rep 21:3781-3793 (2017)

PubMed id: 29281827

Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs.

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.

ABSTRACT

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.