Evidence map›Paper›PMID 30053425›Full record

ArticleCell2018

HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin Downregulation.

Kyle L Morris, Cosmo Z Buffalo, Christina M Stürzel, Elena Heusinger, Frank Kirchhoff, Xuefeng Ren, James H Hurley

Open access · greenAbstract read
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
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  6. A structure-based mechanism for initiation of AP-3 coated vesicle formation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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  10. Journal of medical genetics · 2023
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Kyle L MorrisDepartment of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA.
Cosmo Z BuffaloDepartment of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA.
Christina M StürzelInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Elena HeusingerInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Frank KirchhoffInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Xuefeng RenDepartment of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: snowren@berkeley.edu.
James H HurleyDepartment of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: jimhurley@berkeley.edu.
QB3 · USUniversität Ulm · DEUniversity of California, Berkeley · US

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANKEL, ALAN D · 2007 to 2018
$48.8M
Allostery and Hijacking of Host Membrane Traffic by HIV-1 Accessory ProteinsR01AI120691 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI HURLEY, JAMES H · 2015 to 2024
$6.1M
NIAID NIH HHS R01 AI120691NIGMS NIH HHS P50 GM082250
6 · The paper itself

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.

Indexed as

Adaptor Proteins, Vesicular TransportADP-Ribosylation Factor 1Bone Marrow Stromal Antigen 2ClathrinGolgi ApparatusHEK293 CellsHIV-1Humansnef Gene Products, Human Immunodeficiency VirusProtein TransportTranscription Factor AP-1Adaptor Proteins, Vesicular TransportADP-Ribosylation Factor 1Bone Marrow Stromal Antigen 2Clathrinnef Gene Products, Human Immunodeficiency Virusnef protein, Human immunodeficiency virus 1Transcription Factor AP-1adaptor proteinclathrincryo-EMHIVHIV-Neftrafficking

Identifiers

PMID30053425
PMCPMC6091687
OpenAlexW2884498378

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.