9RTW

Mammalian AP3 complex on tubular membranes (AP3 centered)

Summary for 9RTW

• Entry DOI: 10.2210/pdb9rtw/pdb
• EMDB information: 54255
• Descriptor: AP-3 complex subunit beta, AP-3 complex subunit delta-1, ADP-ribosylation factor 1, ... (5 entities in total)
• Functional Keywords: cargo adapter, coat, trafficking, endocytosis
• Biological source: Pan troglodytes (chimpanzee); More
• Total number of polymer chains: 8
• Total formula weight: 274442.13

Authors

Kaufman, J.G.G.,Tagiltsev, G.,Briggs, J.A.G.,Owen, D.J. (deposition date: 2025-07-03, release date: 2026-05-27)

Primary citation

Kaufman, J.G.G.,Tagiltsev, G.,Stalder, D.S.,Taylor, R.J.,Sava, I.,Guo, H.,Ciazynska, K.A.,Zaccai, N.R.,Gray, S.R.,Vallis, Y.,Honing, S.,Kelly, B.T.,Gershlick, D.C.,Briggs, J.A.G.,Owen, D.J.
Architecture of clathrin-independent AP3:ARF1-coated carriers.
Sci Adv, 12:eaed1529-eaed1529, 2026

PubMed Abstract: The AP3 complex mediates cargo sorting and carrier assembly for the trafficking of transmembrane proteins from endosomes to lysosomes. AP3 is generally believed to localize to clathrin-free, ARF1-positive, elongated carriers in cells, but the architecture of AP3-based coats was unknown. Using in vitro reconstitution and cryo-electron tomography, we demonstrate that AP3:ARF1 spontaneously remodels membranes containing cargo and the phosphoinositide PI(3,5)P into tubular structures coated in spiraling rows of AP3 arches and ARF1 dimers. Targeted point mutations disrupting critical AP3:ARF1 and AP3:AP3 lattice interfaces disrupt AP3 recruitment, carrier formation, and lysosomal cargo trafficking in cells. We propose that AP3 generates tubular carriers on endosomes by organizing ARF1 dimers into elongated membrane-deforming arrays while simultaneously selecting cargo. By demonstrating that AP3:ARF1 can generate carriers without using a clathrin lattice, we explain the clathrin independence of AP3-mediated trafficking.

PubMed: 42139345
DOI: 10.1126/sciadv.aed1529

Experimental method

ELECTRON MICROSCOPY (7.4 Å)