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6D84

Structure of the cargo bound AP-1:Arf1:tetherin-Nef (L164A, L165A) dileucine mutant dimer

Summary for 6D84
Entry DOI10.2210/pdb6d84/pdb
EMDB information7454
DescriptorBone marrow stromal antigen 2,Protein Nef, AP-1 complex subunit beta-1, ADP-ribosylation factor 1, ... (8 entities in total)
Functional Keywordsap, hiv, nef, trafficking, protein transport
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains16
Total formula weight613517.02
Authors
Buffalo, C.Z.,Morris, K.L.,Hurley, J.H. (deposition date: 2018-04-25, release date: 2018-08-08, Last modification date: 2024-03-13)
Primary citationMorris, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (6.72 Å)
Structure validation

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