Evidence map›Paper›PMID 20886905›Full record

ArticleBiochemistry2010

Myristate exposure in the human immunodeficiency virus type 1 matrix protein is modulated by pH.

Emily L Fledderman, Ken Fujii, Ruba H Ghanam, Kayoko Waki, Peter E Prevelige, Eric O Freed, Jamil S Saad

Abstract read
In one paragraph

Article in Biochemistry, 2010. 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
1.4field-weighted citation impact, top 22% 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

32 citing papers in PubMed, 46 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Atomic view of the HIV-1 matrix lattice; implications on virus assembly and envelope incorporation.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. 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

7 authors at 2 institutions in 1 country.

Emily L FleddermanDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Ken Fujii
Ruba H Ghanam
Kayoko Waki
Peter E Prevelige
Eric O Freed
Jamil S Saad
University of Alabama at Birmingham · USFrederick National Laboratory for Cancer Research · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
Retroviral Gag Trafficking, Env Incorporation, and Virus AssemblyZIABC010775 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI FREED, ERIC · 2009 to 2015
$4.6M
Structural basis for HIV-1 Gag interactions with cellular constituentsR01AI087101 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SAAD, JAMIL SUBHI · 2010 to 2014
$1.8M
Retroviral Gag Trafficking, Env Incorporation, and Virus AssemblyZ01BC010775 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI FREED, ERIC · 2007 to 2008
$961k
Howard Hughes Medical InstituteIntramural NIH HHS Z01 BC010775NCI NIH HHS P30 CA013148NCI NIH HHS P30CA13148NIAID NIH HHS R01 AI087101
6 · The paper itself

Abstract

Human immunodeficiency virus type 1 (HIV-1) encodes a polypeptide called Gag that is capable of forming virus-like particles (VLPs) in vitro in the absence of other cellular or viral constituents. During the late phase of HIV-1 infection, Gag polyproteins are transported to the plasma membrane (PM) for assembly. A combination of in vivo, in vitro, and structural studies have shown that Gag targeting and assembly on the PM are mediated by specific interactions between the myristoylated matrix [myr(+)MA] domain of Gag and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Exposure of the MA myristyl (myr) group is triggered by PI(4,5)P2 binding and is enhanced by factors that promote protein self-association. In the studies reported here, we demonstrate that myr exposure in MA is modulated by pH. Our data show that deprotonation of the His89 imidazole ring in myr(+)MA destabilizes the salt bridge formed between His89(Hδ2) and Glu12(COO-), leading to tight sequestration of the myr group and a shift in the equilibrium from trimer to monomer. Furthermore, we show that oligomerization of a Gag-like construct containing matrix-capsid is also pH-dependent. Disruption of the His−Glu salt bridge by single-amino acid substitutions greatly altered the myr-sequestered−myr-exposed equilibrium. In vivo intracellular localization data revealed that the H89G mutation retargets Gag to intracellular compartments and severely inhibits virus production. Our findings reveal that the MA domain acts as a “pH sensor” in vitro, suggesting that the effect of pH on HIV-1 Gag targeting and binding to the PM warrants investigation.

Indexed as

gag Gene Products, Human Immunodeficiency VirusHeLa CellsHIV-1HIV AntigensHIV InfectionsHumansHydrogen-Ion ConcentrationModels, MolecularMutationMyristic AcidNuclear Magnetic Resonance, BiomolecularProtein Multimerizationgag Gene Products, Human Immunodeficiency VirusHIV AntigensMyristic Acidp17 protein, Human Immunodeficiency Virus Type 1

Identifiers

PMID20886905
PMCPMC3032006
OpenAlexW2016864502

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.