9U9R

ARF1(Q71L) bound M4-CTD-undocked AP-4 core

Summary for 9U9R

• Entry DOI: 10.2210/pdb9u9r/pdb
• EMDB information: 63968
• Descriptor: AP-4 complex subunit beta-1, AP-4 complex subunit epsilon-1, ADP-ribosylation factor 1, ... (5 entities in total)
• Functional Keywords: adaptor protein complex, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 220500.59

Authors

Wang, Y.H.,Li, W. (deposition date: 2025-03-29, release date: 2026-03-04, Last modification date: 2026-03-18)

Primary citation

Wang, Y.,Li, W.,Qiu, Y.,Wu, S.,Hong, L.,Zhao, Y.,Feng, W.
Structural basis for the dynamic conformations of AP-4 and its association with ARF1.
Nat Commun, 17:-, 2026

PubMed Abstract: Among the distinct adaptor protein (AP) complexes, AP-4 primarily functions as a non-clathrin-coated vesicle machinery essential for intracellular membrane trafficking. ARF1 is a master regulator of AP-4 membrane recruitment, but the underlying mechanism remains elusive. Here, we present the cryo-EM structures of soluble AP-4 and the AP-4/ARF1 complex. Unexpectedly, AP-4 adopts a dynamic equilibrium between closed and open conformations, caused by loose contacts between its medium subunit and central core. ARF1 binding induces only subtle changes in AP-4, which retains its conformational equilibrium. Mutations at the AP-4/ARF1 interface disrupt complex formation and impair ARF1-dependent membrane recruitment. Efficient membrane recruitment of AP-4 likely requires the synergistic engagement of ARF1 and cargoes. Disrupting the conformational flexibility of AP-4 interferes with this synergistic effect and compromises AP-4-mediated membrane trafficking. Our findings may redefine AP-4 as a conformationally dynamic complex modulated by cooperative interactions, providing insights into neurodevelopmental disorders associated with AP-4 dysfunction.

PubMed: 41565640
DOI: 10.1038/s41467-026-68679-8

Experimental method

ELECTRON MICROSCOPY (6.6 Å)