6DFF

Structure of the cargo bound AP-1:Arf1:tetherin-Nef monomer

Summary for 6DFF

• Entry DOI: 10.2210/pdb6dff/pdb
• EMDB information: 7455
• Descriptor: Bone marrow stromal antigen 2, Nef protein chimera, AP-1 complex subunit beta-1, ADP-ribosylation factor 1, ... (8 entities in total)
• Functional Keywords: ap, hiv, nef, trafficking, viral protein, protein transport, transport protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 306926.83

Authors

Morris, K.L.,Buffalo, C.Z.,Ren, X.,Hurley, J.H. (deposition date: 2018-05-14, release date: 2018-08-08, Last modification date: 2024-03-13)

Primary citation

Morris, K.L.,Buffalo, C.Z.,Sturzel, C.M.,Heusinger, E.,Kirchhoff, F.,Ren, X.,Hurley, J.H.
HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin Downregulation.
Cell, 174:659-671.e14, 2018

PubMed Abstract: The HIV accessory protein Nef counteracts immune defenses by subverting coated vesicle pathways. The 3.7 Å cryo-EM structure of a closed trimer of the clathrin adaptor AP-1, the small GTPase Arf1, HIV-1 Nef, and the cytosolic tail of the restriction factor tetherin suggested a mechanism for inactivating tetherin by Golgi retention. The 4.3 Å structure of a mutant Nef-induced dimer of AP-1 showed how the closed trimer is regulated by the dileucine loop of Nef. HDX-MS and mutational analysis were used to show how cargo dynamics leads to alternative Arf1 trimerization, directing Nef targets to be either retained at the trans-Golgi or sorted to lysosomes. Phosphorylation of the NL4-3 M-Nef was shown to regulate AP-1 trimerization, explaining how O-Nefs lacking this phosphosite counteract tetherin but most M-Nefs do not. These observations show how the higher-order organization of a vesicular coat can be allosterically modulated to direct cargoes to distinct fates.

PubMed: 30053425
DOI: 10.1016/j.cell.2018.07.004

Experimental method

ELECTRON MICROSCOPY (3.9 Å)