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| Title | Structural basis for the dynamic conformations of AP-4 and its association with ARF1. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 17, Issue 1, Year 2026 |
| Publish date | Jan 21, 2026 |
Authors | Yanghui Wang / Wei Li / Yunlong Qiu / Si Wu / Liu Hong / Yan Zhao / Wei Feng / ![]() |
| 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 ...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. |
External links | Nat Commun / PubMed:41565640 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.0 - 6.8 Å |
| Structure data | EMDB-63965, PDB-9u9i: EMDB-63966, PDB-9u9j: EMDB-63968, PDB-9u9r: EMDB-63969, PDB-9u9s: |
| Source |
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Keywords | PROTEIN TRANSPORT / adaptor protein complex / cargo transportation / AP-4 complex / TRANSPORT PROTEIN |
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