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-Structure paper
タイトル | HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin Downregulation. |
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ジャーナル・号・ページ | Cell, Vol. 174, Issue 3, Page 659-671.e14, Year 2018 |
掲載日 | 2018年7月26日 |
著者 | Kyle L Morris / Cosmo Z Buffalo / Christina M Stürzel / Elena Heusinger / Frank Kirchhoff / Xuefeng Ren / James H Hurley / |
PubMed 要旨 | 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, ...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. |
リンク | Cell / PubMed:30053425 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.73 - 6.8 Å |
構造データ | EMDB-7453: Structure of the HIV-Nef dileucine mutant bound AP-1:Arf1 dimer monomeric subunit EMDB-7454: Structure of the HIV-Nef dileucine mutant bound AP-1:Arf1 dimer EMDB-7455, PDB-6dff: EMDB-7456: EMDB-7457: Structure of the HIV-Nef bound AP-1:Arf1 closed trimer monomeric subunit EMDB-7458: |
化合物 | ChemComp-GTP: ChemComp-MG: |
由来 |
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キーワード | VIRAL PROTEIN (ウイルスタンパク質) / PROTEIN TRANSPORT / AP / HIV (ヒト免疫不全ウイルス) / Nef / trafficking / TRANSPORT PROTEIN (運搬体タンパク質) |