Evidence map›Paper›PMID 38789685›Full record

ArticleNature structural & molecular biology2024

Structural insights into PPP2R5A degradation by HIV-1 Vif.

Yingxia Hu, Krista A Delviks-Frankenberry, Chunxiang Wu, Fidel Arizaga, Vinay K Pathak, Yong Xiong

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Yingxia Hu *Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Krista A Delviks-Frankenberry *Viral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
Chunxiang WuDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8635-1578
Fidel ArizagaDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Vinay K PathakViral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA. vinay.pathak@nih.gov.ORCID http://orcid.org/0000-0003-2441-8412
Yong XiongDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. yong.xiong@yale.edu.ORCID http://orcid.org/0000-0001-9625-9313

Funding

Structure and Function of Vif and APOBEC3 (A3) ProteinsZIABC010595 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PATHAK, VINAY K. · 2009 to 2025
$14.8M
PREDOCTORAL PROGRAM IN BIOPHYSICST32GM008283 · NIGMS · YALE UNIVERSITY · PI XIONG, YONG · 1988 to 2022
$10.5M
Multifaceted interactions between lentiviral Vif and host molecules for viral infectivity enhancementR37AI116313 · NIAID · YALE UNIVERSITY · PI Yong Xiong · 2021 to 2026
$3.2M
Predoctoral Program in BiophysicsT32GM149438 · NIGMS · YALE UNIVERSITY · PI Yong Xiong, Elsa Chui Ying Yan · 2023 to 2026
$2.6M
NIAID NIH HHS R37 AI116313NIGMS NIH HHS T32 GM008283NIGMS NIH HHS T32 GM149438
6 · The paper itself

Abstract

HIV-1 Vif recruits host cullin-RING-E3 ubiquitin ligase and CBFβ to degrade the cellular APOBEC3 antiviral proteins through diverse interactions. Recent evidence has shown that Vif also degrades the regulatory subunits PPP2R5(A-E) of cellular protein phosphatase 2A to induce G2/M cell cycle arrest. As PPP2R5 proteins bear no functional or structural resemblance to A3s, it is unclear how Vif can recognize different sets of proteins. Here we report the cryogenic-electron microscopy structure of PPP2R5A in complex with HIV-1 Vif-CBFβ-elongin B-elongin C at 3.58 Å resolution. The structure shows PPP2R5A binds across the Vif molecule, with biochemical and cellular studies confirming a distinct Vif-PPP2R5A interface that partially overlaps with those for A3s. Vif also blocks a canonical PPP2R5A substrate-binding site, indicating that it suppresses the phosphatase activities through both degradation-dependent and degradation-independent mechanisms. Our work identifies critical Vif motifs regulating the recognition of diverse A3 and PPP2R5A substrates, whereby disruption of these host-virus protein interactions could serve as potential targets for HIV-1 therapeutics.

Indexed as

Cryoelectron MicroscopyHIV-1Models, MolecularProtein Phosphatase 2vif Gene Products, Human Immunodeficiency VirusBinding SitesCore Binding Factor beta SubunitElonginHEK293 CellsHumansProtein BindingProtein ConformationProteolysisTranscription FactorsCBFB protein, humanCore Binding Factor beta SubunitELOC protein, humanElonginPPP2R5A protein, humanProtein Phosphatase 2Transcription Factorsvif Gene Products, Human Immunodeficiency Virusvif protein, Human immunodeficiency virus 1

Identifiers

PMID38789685
PMCPMC12221852

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Registered trials

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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.