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-Structure paper
| Title | Architecture of clathrin-independent AP3:ARF1-coated carriers. |
|---|---|
| Journal, issue, pages | Sci Adv, Vol. 12, Issue 20, Page eaed1529, Year 2026 |
| Publish date | May 15, 2026 |
Authors | Jonathan G G Kaufman / Grigory Tagiltsev / Danièle S Stalder / Rebecca J Taylor / Ioana Sava / Hui Guo / Katarzyna A Ciazynska / Nathan R Zaccai / Sally R Gray / Yvonne Vallis / Stefan Höning / Bernard T Kelly / David C Gershlick / John A G Briggs / David J Owen / ![]() |
| 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- ...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. |
External links | Sci Adv / PubMed:42139345 / PubMed Central |
| Methods | EM (subtomogram averaging) |
| Resolution | 7.4 - 13.0 Å |
| Structure data | EMDB-54255, PDB-9rtw: EMDB-54256, PDB-9rtx: EMDB-54257, PDB-9rty: EMDB-54258, PDB-9rtz: |
| Source |
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Keywords | ENDOCYTOSIS / Cargo adapter / Coat / trafficking |
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