5YPO

Crystal structure of PSD-95 GK domain in complex with phospho-SAPAP peptide

Summary for 5YPO

• Entry DOI: 10.2210/pdb5ypo/pdb
• Descriptor: Disks large homolog 4, SAPAP, GLYCEROL, ... (4 entities in total)
• Functional Keywords: psd-95 sapap phosphorylation synapse, protein binding
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Cell membrane ; Lipid-anchor ; Cytoplasmic side : P31016
• Total number of polymer chains: 4
• Total formula weight: 47204.92

Authors

Zhu, J.,Zhou, Q.,Shang, Y.,Weng, Z.,Zhang, R.,Zhang, M. (deposition date: 2017-11-02, release date: 2018-03-14, Last modification date: 2024-11-20)

Primary citation

Zhu, J.,Zhou, Q.,Shang, Y.,Li, H.,Peng, M.,Ke, X.,Weng, Z.,Zhang, R.,Huang, X.,Li, S.S.C.,Feng, G.,Lu, Y.,Zhang, M.
Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs.
Cell Rep, 21:3781-3793, 2017

PubMed 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.

PubMed: 29281827
DOI: 10.1016/j.celrep.2017.11.107

Experimental method

X-RAY DIFFRACTION (2.29 Å)