Evidence map›Paper›PMID 17920628›Full record

ArticleJournal of molecular biology2007

Allosteric loss-of-function mutations in HIV-1 Nef from a long-term non-progressor.

Ronald P Trible, Lori Emert-Sedlak, Thomas E Wales, Velpandi Ayyavoo, John R Engen, Thomas E Smithgall

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Article
  6. Dynamics of the Tec-family tyrosine kinase SH3 domains.Protein science : a publication of the Protein Society · 2016
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Mechanisms of HIV-1 Nef function and intracellular signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2011
    Review
  17. Article
  18. Article
  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

6 authors at 2 institutions in 1 country.

Ronald P TribleMolecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Lori Emert-Sedlak
Thomas E Wales
Velpandi Ayyavoo
John R Engen
Thomas E Smithgall
University of Pittsburgh · USNortheastern University · US

Funding

Small Molecule Inhibitors of HIV Nef SignalingR01AI057083 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SMITHGALL, THOMAS E. · 2003 to 2019
$5.1M
SRC FAMILY KINASES AS MOLECULAR TARGETS FOR HIV NEFR01CA081398 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SMITHGALL, THOMAS E. · 1998 to 2010
$1.8M
Structural Dynamics of Src-Family Kinase ActivationR01GM070590 · NIGMS · UNIVERSITY OF NEW MEXICO · PI ENGEN, JOHN R · 2004 to 2008
$1.5M
NCI NIH HHS CA81398NCI NIH HHS R01 CA081398NIAID NIH HHS AI57083NIAID NIH HHS R01 AI057083NIGMS NIH HHS GM070590NIGMS NIH HHS R01 GM070590
6 · The paper itself

Abstract

Activation of Src family kinases by human immunodeficiency virus type 1 (HIV-1) Nef may play an important role in the pathogenesis of HIV/AIDS. Here we investigated whether diverse Nef sequences universally activate Hck, a Src family member expressed in macrophages and other HIV-1 target cells. In general, we observed that Hck activation is a highly conserved Nef function. However, we identified an unusual Nef variant from an HIV-positive individual that did not develop AIDS which failed to activate Hck despite the presence of conserved residues linked to Hck SH3 domain binding and kinase activation. Amino acid sequence alignment with active Nef proteins revealed differences in regions not previously implicated in Hck activation, including a large internal flexible loop absent from available Nef structures. Substitution of these residues in active Nef compromised Hck activation without affecting SH3 domain binding. These findings show that residues at a distance from the SH3 domain binding site influence Nef interactions allosterically with a key effector protein linked to AIDS progression.

Indexed as

Allosteric RegulationCells, CulturedDeuterium Exchange MeasurementDimerizationGreen Fluorescent ProteinsHIV-1HumansImmunoblottingMass SpectrometryMutationnef Gene Products, Human Immunodeficiency VirusProtein ConformationProto-Oncogene Proteins c-hckRecombinant Fusion ProteinsSaccharomyces cerevisiaeTransformation, Geneticenhanced green fluorescent proteinGreen Fluorescent Proteinsnef Gene Products, Human Immunodeficiency VirusProto-Oncogene Proteins c-hckRecombinant Fusion Proteins

Identifiers

PMID17920628
PMCPMC2117379
OpenAlexW2077682177

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.