9DDS

Crystal structure of human AAGAB G domain with E144K mutation

Summary for 9DDS

• Entry DOI: 10.2210/pdb9dds/pdb
• Descriptor: Alpha- and gamma-adaptin-binding protein p34 (2 entities in total)
• Functional Keywords: adaptin; complex; membrane transfer, protein binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 39350.59

Authors

Wang, B.,Tian, Y.,Yin, Q. (deposition date: 2024-08-28, release date: 2025-07-16, Last modification date: 2026-01-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.78 Å)