Evidence map›Paper›PMID 30333189›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5α identified by magic-angle spinning NMR and molecular dynamics simulations.

Caitlin M Quinn, Mingzhang Wang, Matthew P Fritz, Brent Runge, Jinwoo Ahn, Chaoyi Xu, Juan R Perilla, Angela M Gronenborn, Tatyana Polenova

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Understanding Virus Structure and Dynamics through Molecular Simulations.Journal of chemical theory and computation · 2023
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
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  12. Article
  13. Review
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  15. Review
  16. Physics of viral dynamics.Nature reviews. Physics · 2021
    Review
  17. Review
  18. Article
  19. Review
  20. 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

9 authors.

Caitlin M QuinnDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716.
Mingzhang WangDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716.
Matthew P FritzDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716.
Brent RungeDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716.
Jinwoo AhnPittsburgh Center for HIV Protein Interactions, University of Pittsburgh, Pittsburgh, PA 15260.
Chaoyi XuDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716.
Juan R PerillaDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716; jperilla@udel.edu amg100@pitt.edu tpolenov@udel.edu.ORCID 0000-0003-1171-6816
Angela M GronenbornPittsburgh Center for HIV Protein Interactions, University of Pittsburgh, Pittsburgh, PA 15260; jperilla@udel.edu amg100@pitt.edu tpolenov@udel.edu.ORCID 0000-0001-9072-3525
Tatyana PolenovaDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716; jperilla@udel.edu amg100@pitt.edu tpolenov@udel.edu.ORCID 0000-0002-0346-1131

Funding

X-Ray Core P50GM082251 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ENGELMAN, ALAN N. · 2007 to 2018
$48.1M
Technology Development 2: MAS NMR and dynamic nuclear polarization for HIV-1 structural biologyP50AI150481 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRONENBORN, ANGELA M. · 2019 to 2021
$14.1M
Pilot Research Subproject ProgramP30GM110758 · NIGMS · UNIVERSITY OF DELAWARE · PI PATEL, SANDEEP · 2014 to 2018
$5.8M
COBRE on Membrane Protein Production and CharacterizationP30GM103519 · NIGMS · UNIVERSITY OF DELAWARE · PI LENHOFF, ABRAHAM M · 2012 to 2014
$3.3M
MAS NMR Studies of the NIV-1 Gag Polyprotein Assembled into Virus-Like ParticlesF32GM113452 · NIGMS · UNIVERSITY OF DELAWARE · PI QUINN, CAITLIN · 2015 to 2016
$109k
NIAID NIH HHS P50 AI150481NIGMS NIH HHS F32 GM113452NIGMS NIH HHS P30 GM103519NIGMS NIH HHS P30 GM110758NIGMS NIH HHS P50 GM082251
6 · The paper itself

Abstract

The host factor protein TRIM5α plays an important role in restricting the host range of HIV-1, interfering with the integrity of the HIV-1 capsid. TRIM5 triggers an antiviral innate immune response by functioning as a capsid pattern recognition receptor, although the precise mechanism by which the restriction is imposed is not completely understood. Here we used an integrated magic-angle spinning nuclear magnetic resonance and molecular dynamics simulations approach to characterize, at atomic resolution, the dynamics of the capsid's hexameric and pentameric building blocks, and the interactions with TRIM5α in the assembled capsid. Our data indicate that assemblies in the presence of the pentameric subunits are more rigid on the microsecond to millisecond timescales than tubes containing only hexamers. This feature may be of key importance for controlling the capsid's morphology and stability. In addition, we found that TRIM5α binding to capsid induces global rigidification and perturbs key intermolecular interfaces essential for higher-order capsid assembly, with structural and dynamic changes occurring throughout the entire CA polypeptide chain in the assembly, rather than being limited to a specific protein-protein interface. Taken together, our results suggest that TRIM5α uses several mechanisms to destabilize the capsid lattice, ultimately inducing its disassembly. Our findings add to a growing body of work indicating that dynamic allostery plays a pivotal role in capsid assembly and HIV-1 infectivity.

Indexed as

Amino Acid SequenceAnimalsBinding SitesCapsidCapsid ProteinsCloning, MolecularEscherichia coliGene ExpressionGenetic VectorsHIV-1HumansMacaca mulattaMagnetic Resonance SpectroscopyMolecular Dynamics SimulationProtein BindingProtein Conformation, alpha-HelicalCapsid ProteinsProteinsRecombinant ProteinsTRIM5(alpha) protein, rhesus monkeyUbiquitin-Protein LigasesCA protein assembliesHIV-1 capsidHIV-AIDSmagic-angle spinning NMRTRIM5α

Identifiers

PMID30333189
PMCPMC6233135

What OpenQuestion holds

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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.