Evidence map›Paper›PMID 30961890›Full record

ArticleBiophysical journal2019

Conformational Dynamics of the HIV-Vif Protein Complex.

K Aurelia Ball, Lieza M Chan, David J Stanley, Elise Tierney, Sampriti Thapa, Hai M Ta, Lily Burton, Jennifer M Binning, Matthew P Jacobson, John D Gross

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biophysical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 34% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Article
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

10 authors at 2 institutions in 1 country.

K Aurelia BallDepartment of Chemistry, Skidmore College, Saratoga Springs, New York. Electronic address: kball@skidmore.edu.
Lieza M ChanDepartment of Chemistry, Skidmore College, Saratoga Springs, New York.
David J StanleyDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.
Elise TierneyDepartment of Chemistry, Skidmore College, Saratoga Springs, New York.
Sampriti ThapaDepartment of Chemistry, Skidmore College, Saratoga Springs, New York.
Hai M TaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.
Lily BurtonDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.
Jennifer M BinningDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.
Matthew P JacobsonDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.
John D GrossDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California. Electronic address: jdgross@cgl.ucsf.edu.
University of California, San Francisco · USSkidmore College · US

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANKEL, ALAN D · 2007 to 2018
$48.8M
Structure and Function of the Decapping Enzyme ComplexR01GM078360 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GROSS, JOHN D · 2009 to 2018
$2.5M
Evolution of the Vif E3 Ubiquitin LigaseF32AI120867 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BINNING, JENNIFER · 2016 to 2018
$141k
Investigating HIV Vif Interactions with Host ProteinsF32GM114894 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BALL, KATHERINE AURELIA · 2015 to 2016
$80k
NIAID NIH HHS F32 AI120867NIGMS NIH HHS F32 GM114894NIGMS NIH HHS P50 GM082250NIGMS NIH HHS R01 GM078360
6 · The paper itself

Abstract

Human immunodeficiency virus-1 viral infectivity factor (Vif) is an intrinsically disordered protein responsible for the ubiquitination of the APOBEC3 (A3) antiviral proteins. Vif folds when it binds Cullin-RING E3 ligase 5 and the transcription cofactor CBF-β. A five-protein complex containing the substrate receptor (Vif, CBF-β, Elongin-B, Elongin-C (VCBC)) and Cullin5 (CUL5) has a published crystal structure, but dynamics of this VCBC-CUL5 complex have not been characterized. Here, we use molecular dynamics (MD) simulations and NMR to characterize the dynamics of the VCBC complex with and without CUL5 and an A3 protein bound. Our simulations show that the VCBC complex undergoes global dynamics involving twisting and clamshell opening of the complex, whereas VCBC-CUL5 maintains a more static conformation, similar to the crystal structure. This observation from MD is supported by methyl-transverse relaxation-optimized spectroscopy NMR data, which indicates that the VCBC complex without CUL5 is dynamic on the μs-ms timescale. Our NMR data also show that the VCBC complex is more conformationally restricted when bound to the antiviral APOBEC3F (one of the A3 proteins), consistent with our MD simulations. Vif contains a flexible linker region located at the hinge of the VCBC complex, which changes conformation in conjunction with the global dynamics of the complex. Like other substrate receptors, VCBC can exist alone or in complex with CUL5 and other proteins in cells. Accordingly, the VCBC complex could be a good target for therapeutics that would inhibit full assembly of the ubiquitination complex by stabilizing an alternate VCBC conformation.

Indexed as

Molecular Dynamics SimulationAPOBEC DeaminasesCore Binding Factor beta SubunitCrystallizationCullin ProteinsCytidine DeaminaseElonginHumansKineticsProtein BindingProtein ConformationProtein FoldingStructure-Activity RelationshipUbiquitinationvif Gene Products, Human Immunodeficiency VirusAPOBEC3 proteins, humanAPOBEC DeaminasesCBFB protein, humanCore Binding Factor beta SubunitCullin ProteinsCytidine DeaminaseELOC protein, humanElonginvif Gene Products, Human Immunodeficiency Virusvif protein, Human immunodeficiency virus 1

Identifiers

PMID30961890
PMCPMC6486493
OpenAlexW2903444460

What OpenQuestion holds

Textmetadata
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.