Evidence map›Paper›PMID 18653452›Full record

ArticleJournal of virology2008

Functional characterization of the human immunodeficiency virus type 1 Nef acidic domain.

Laura L Baugh, J Victor Garcia, John L Foster

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

16 citing papers in PubMed, 29 citations in OpenAlex.

  1. Structural basis of CD4 downregulation by HIV-1 Nef.Nature structural & molecular biology · 2020
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Protein intrinsic disorder as a flexible armor and a weapon of HIV-1.Cellular and molecular life sciences : CMLS · 2012
    Review
  10. Review
  11. Mechanisms of HIV-1 Nef function and intracellular signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2011
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Laura L BaughY9.206, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
J Victor Garcia
John L Foster
The University of Texas Southwestern Medical Center · US

Funding

NEF FUNCTIONR01AI033331 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GARCIA-MARTINEZ, J. VICTOR · 1994 to 2010
$4.4M
NIAID NIH HHS AI-33331NIAID NIH HHS R01 AI033331
6 · The paper itself

Abstract

The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef downregulates major histocompatibility complex class I (MHC-I) from the cell surface. It has been proposed that the direct interaction of the acidic cluster (AC) of Nef, (62)EEEE(65), with the furin binding region (fbr) of PACS-1 is crucial for this Nef function. Contrary to this proposal, evidence is presented here that the four glutamates in Nef do not functionally engage the PACS-1 fbr. (i) The binding of Nef to the PACS-1 fbr in vitro is much weaker than the binding of the canonical furin AC to the PACS-1 fbr. (ii) The mutation of two of the four glutamates in Nef's AC to alanines does not alter Nef's ability to downregulate MHC-I, and triply mutated Nefs exhibit 50% activity. (iii) The introduction of lysine into the AC has little effect on Nef function. (iv) The mutation of all four glutamates to alanine does debilitate Nef MHC-I downregulation, but this quadruple mutation also impairs the ability of Nef to regulate p21-activated protein kinase and enhance viral particle infectivity. (v) The replacement of the Nef AC with the bona fide AC from furin results in the loss of the expected regulatory properties of the furin AC. (vi) The insertion of the conformation-disrupting amino acid proline into the Nef AC does not disrupt MHC-I downregulation. Our results are consistent with an alternative model in which (62)EEEE(65) plays a stabilizing role in the formation of a ternary complex between Nef, the MHC-I cytoplasmic domain, and AP-1.

Indexed as

Gene Expression Regulation, ViralAmino Acid SequenceGene Products, nefHeLa CellsHistocompatibility Antigens Class IHIV-1HumansModels, MolecularMolecular ConformationMolecular Sequence DataMutagenesis, Site-DirectedMutationProtein BindingProtein Structure, TertiaryTranscription Factor AP-1Gene Products, nefHistocompatibility Antigens Class ITranscription Factor AP-1

Identifiers

PMID18653452
PMCPMC2546962
OpenAlexW2148845590

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.