5IZU

A new binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function

5IZU の概要

• エントリーDOI: 10.2210/pdb5izu/pdb
• 分子名称: SH3 and multiple ankyrin repeat domains protein 3, peptide from Disks large-associated protein 3 (3 entities in total)
• 機能のキーワード: shank, sapap, pdz, extension, synapse, specific interaction, protein binding
• 由来する生物種: Mus musculus (Mouse); 詳細
• 細胞内の位置: Cytoplasm: Q4ACU6; Cell membrane ; Peripheral membrane protein : Q6PFD5
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 34570.93

構造登録者

Shang, Y.,Zeng, M.,Zhang, M. (登録日: 2016-03-26, 公開日: 2016-05-18, 最終更新日: 2023-11-08)

主引用文献

Zeng, M.,Shang, Y.,Guo, T.,He, Q.,Yung, W.H.,Liu, K.,Zhang, M.
A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function
Proc.Natl.Acad.Sci.USA, 113:E3081-E3090, 2016

PubMed Abstract: Shank and SAPAP (synapse-associated protein 90/postsynaptic density-95-associated protein) are two highly abundant scaffold proteins that directly interact with each other to regulate excitatory synapse development and plasticity. Mutations of SAPAP, but not other reported Shank PDZ domain binders, share a significant overlap on behavioral abnormalities with the mutations of Shank both in patients and in animal models. The molecular mechanism governing the exquisite specificity of the Shank/SAPAP interaction is not clear, however. Here we report that a sequence preceding the canonical PDZ domain of Shank, together with the elongated PDZ BC loop, form another binding site for a sequence upstream of the SAPAP PDZ-binding motif, leading to a several hundred-fold increase in the affinity of the Shank/SAPAP interaction. We provide evidence that the specific interaction afforded by this newly identified site is required for Shank synaptic targeting and the Shank-induced synaptic activity increase. Our study provides a molecular explanation of how Shank and SAPAP dosage changes due to their gene copy number variations can contribute to different psychiatric disorders.

PubMed: 27185935
DOI: 10.1073/pnas.1523265113

実験手法

X-RAY DIFFRACTION (2.494 Å)