Evidence map›Paper›PMID 33397805›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as potential substrates for proteolytic maturation.

Aaron Tan, Alexander J Pak, Dustin R Morado, Gregory A Voth, John A G Briggs

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. 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. Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026
    Review
  2. Article
  3. Article
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  7. Membrane bending energy selects for compact growth of protein assemblies.bioRxiv : the preprint server for biology · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Journal of chemical theory and computation · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Understanding Virus Structure and Dynamics through Molecular Simulations.Journal of chemical theory and computation · 2023
    Review
  19. Article
  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

5 authors.

Aaron TanStructural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, CB2 0QH Cambridge, United Kingdom.ORCID 0000-0002-4046-7380
Alexander J PakDepartment of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, Chicago, IL 60637.ORCID 0000-0003-2823-6480
Dustin R MoradoStructural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, CB2 0QH Cambridge, United Kingdom.
Gregory A VothDepartment of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, Chicago, IL 60637; gavoth@uchicago.edu jbriggs@mrc-lmb.cam.ac.uk.ORCID 0000-0002-3267-6748
John A G BriggsStructural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, CB2 0QH Cambridge, United Kingdom; gavoth@uchicago.edu jbriggs@mrc-lmb.cam.ac.uk.ORCID 0000-0003-3990-6910

Funding

Structure Analysis of Viral Assembly MechanismsR01AI150492 · NIAID · UNIVERSITY OF VIRGINIA · PI YEAGER, MARK JAY · 2020 to 2021
$1.2M
Computational Insights into Assembly, Budding, and Maturation during HIV-1 ReplicationF32AI150477 · NIAID · UNIVERSITY OF CHICAGO · PI PAK, ALEXANDER · 2019 to 2019
$64k
Medical Research Council MC_UP_1201/16NIAID NIH HHS F32 AI150477NIAID NIH HHS R01 AI150492
6 · The paper itself

Abstract

The CA (capsid) domain of immature HIV-1 Gag and the adjacent spacer peptide 1 (SP1) play a key role in viral assembly by forming a lattice of CA hexamers, which adapts to viral envelope curvature by incorporating small lattice defects and a large gap at the site of budding. This lattice is stabilized by intrahexameric and interhexameric CA-CA interactions, which are important in regulating viral assembly and maturation. We applied subtomogram averaging and classification to determine the oligomerization state of CA at lattice edges and found that CA forms partial hexamers. These structures reveal the network of interactions formed by CA-SP1 at the lattice edge. We also performed atomistic molecular dynamics simulations of CA-CA interactions stabilizing the immature lattice and partial CA-SP1 helical bundles. Free energy calculations reveal increased propensity for helix-to-coil transitions in partial hexamers compared to complete six-helix bundles. Taken together, these results suggest that the CA dimer is the basic unit of lattice assembly, partial hexamers exist at lattice edges, these are in a helix-coil dynamic equilibrium, and partial helical bundles are more likely to unfold, representing potential sites for HIV-1 maturation initiation.

Indexed as

CapsidCapsid ProteinsCrystallography, X-Raygag Gene Products, Human Immunodeficiency VirusHIV-1HIV InfectionsHIV SeropositivityHumansMolecular Dynamics SimulationProtein MultimerizationProteolysisSp1 Transcription FactorVirionVirus AssemblyCapsid Proteinsgag Gene Products, Human Immunodeficiency VirusSp1 Transcription Factorcryo-electron tomographyHIV-1maturationmolecular dynamics simulationsvirus assembly

Identifiers

PMID33397805
PMCPMC7826355

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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.