9DDS

Crystal structure of human AAGAB G domain with E144K mutation

9DDS の概要

• エントリーDOI: 10.2210/pdb9dds/pdb
• 分子名称: Alpha- and gamma-adaptin-binding protein p34 (2 entities in total)
• 機能のキーワード: adaptin; complex; membrane transfer, protein binding
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39350.59

構造登録者

Wang, B.,Tian, Y.,Yin, Q. (登録日: 2024-08-28, 公開日: 2025-07-16, 最終更新日: 2026-01-28)

主引用文献

Wang, B.,Yang, R.,Wan, C.,Tian, Y.,Wu, J.,Adewole, T.S.,Roy, S.,Li, S.,Shen, J.,Yin, Q.
Structural basis of pseudoGTPase-mediated protein-protein interactions.
Structure, 33:1676-1687.e5, 2025

PubMed Abstract: GTPases regulate cellular processes through conformational changes triggered by guanine nucleotide binding. Recently, pseudoGTPases, the catalytically inactive counterparts of GTPases, have been identified across species from bacteria to human, although their functions and mechanisms remain unexplored. Here, we demonstrate that the N-terminal region of the assembly chaperone AAGAB is a class I pseudoGTPase using biochemistry and X-ray crystallography. Furthermore, we discovered that the AAGAB pseudoGTPase domain (psGD) interacts with the σ subunits of AP1 and AP2 adaptor complexes, which are heterotetrameric complexes involved in clathrin-mediated membrane trafficking. AAGAB psGD engages the σ subunits via a unique interface distinct from the conventional GTPase interacting regions. Further biochemical and cell-based assays confirmed the crucial role of the newly identified interface in binding and membrane trafficking. Collectively, our results establish AAGAB pseudoGTPase domain as a critical protein-protein interaction module. These findings offer new insight into the structural basis and molecular mechanisms of pseudoGTPases.

PubMed: 40752490
DOI: 10.1016/j.str.2025.07.009

実験手法

X-RAY DIFFRACTION (1.78 Å)