6KYK

Crystal structure of Shank3 NTD-ANK mutant in complex with Rap1

6KYK の概要

• エントリーDOI: 10.2210/pdb6kyk/pdb
• 関連するPDBエントリー: 6KYH
• 分子名称: SH3 and multiple ankyrin repeat domains protein 3, Ras-related protein Rap-1b, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: shank3, gtpase, synaptic scaffold protein, structural protein-signaling protein complex, structural protein/signaling protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 162226.76

構造登録者

Cai, Q.,Zhang, M. (登録日: 2019-09-19, 公開日: 2019-12-04, 最終更新日: 2024-10-16)

主引用文献

Cai, Q.,Hosokawa, T.,Zeng, M.,Hayashi, Y.,Zhang, M.
Shank3 Binds to and Stabilizes the Active Form of Rap1 and HRas GTPases via Its NTD-ANK Tandem with Distinct Mechanisms.
Structure, 28:290-, 2020

PubMed Abstract: Shank1/2/3, major scaffold proteins in excitatory synapses, are frequently mutated in patients with psychiatric disorders. Although the Shank N-terminal domain and ankyrin repeats domain tandem (NTD-ANK) is known to bind to Ras and Rap1, the molecular mechanism underlying and functional significance of the bindings in synapses are unknown. Here, we demonstrate that Shank3 NTD-ANK specifically binds to the guanosine triphosphate (GTP)-bound form of HRas and Rap1. In addition to the canonical site mediated by the Ras-association domain and common to both GTPases, Shank3 contains an unconventional Rap1 binding site formed by NTD and ANK together. Binding of Shank3 to the GTP-loaded Rap1 slows down its GTP hydrolysis by SynGAP. We further show that the interactions between Shank3 and HRas/Rap1 at excitatory synapses are promoted by synaptic activation. Thus, Shank3 may be able to modulate signaling of the Ras family proteins via directly binding to and stabilizing the GTP-bound form of the enzymes.

PubMed: 31879129
DOI: 10.1016/j.str.2019.11.018

実験手法

X-RAY DIFFRACTION (2.82 Å)