5YPO

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

5YPO の概要

• エントリーDOI: 10.2210/pdb5ypo/pdb
• 分子名称: Disks large homolog 4, SAPAP, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: psd-95 sapap phosphorylation synapse, protein binding
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• 細胞内の位置: Cell membrane ; Lipid-anchor ; Cytoplasmic side : P31016
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 47204.92

構造登録者

Zhu, J.,Zhou, Q.,Shang, Y.,Weng, Z.,Zhang, R.,Zhang, M. (登録日: 2017-11-02, 公開日: 2018-03-14, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.29 Å)