Evidence map›Paper›PMID 23966389›Full record

ArticleJournal of virology2013

A functional interaction between gp41 and gp120 is observed for monomeric but not oligomeric, uncleaved HIV-1 Env gp140.

Miklos Guttman, Kelly K Lee

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016
    Pooled it
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  20. Stable, uncleaved HIV-1 envelope glycoprotein gp140 forms a tightly folded trimer with a native-like structure.Proceedings of the National Academy of Sciences of the United States of America · 2014
    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

2 authors at 1 institution in 1 country.

Miklos GuttmanDepartment of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.
Kelly K Lee
University of Washington · US

Funding

Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI OLAF KUTSCH · 1988 to 2026
$84.1M
ZWITTERION SURFACTANT DDMAB FOR IMPROV STABIL OF PROTEINP41RR001209 · NCRR · STANFORD UNIVERSITY · PI GONZALEZ, ANA M · 1985 to 2011
$38.9M
Waters ACQUITY UPLC M-Class with NanoLockSpray ionization sourceR01GM099989 · NIGMS · UNIVERSITY OF WASHINGTON · PI LEE, KELLY KEISEN · 2012 to 2020
$3.5M
Influenza Hemagglutinin: Structure, Dynamics, and Cooperativity During FusionR00GM080352 · NIGMS · UNIVERSITY OF WASHINGTON · PI LEE, KELLY KEISEN · 2009 to 2011
$740k
Investigating the Architecture of HIV Envelope GlycoproteinF32GM097805 · NIGMS · UNIVERSITY OF WASHINGTON · PI GUTTMAN, MIKLOS · 2012 to 2013
$101k
NCRR NIH HHS P41 RR001209NCRR NIH HHS P41-RR001209NIAID NIH HHS P30 AI027767NIGMS NIH HHS F32 GM097805NIGMS NIH HHS F32-GM097805NIGMS NIH HHS R00 GM080352NIGMS NIH HHS R00-GM080352NIGMS NIH HHS R01 GM099989NIGMS NIH HHS R01-GM099989
6 · The paper itself

Abstract

The envelope glycoprotein (Env) is the sole antigenic feature on the surface of HIV and the target for the humoral immune system. Soluble, uncleaved gp140 Env constructs truncated at the transmembrane domain are being investigated intensively as potential vaccine immunogens by many groups, and understanding their structural properties is essential. We used hydrogen/deuterium-exchange mass spectrometry and small-angle X-ray scattering to probe structural order in a panel of commonly used gp140 constructs and matched gp120 monomers. We observed that oligomeric forms of uncleaved gp140, generally presumed to be trimeric, contain a protease-resistant form of gp41 akin to the postfusion, helical bundle conformation and appear to lack specific interactions between gp120 and gp41. In contrast, the monomeric form of gp140 shows significant stabilization of the gp120 inner domain imparted by the gp41 region, demonstrating excellent agreement with past mutagenesis studies. Moreover, the gp140 monomers respond to CD4 binding in manner that is consistent with the initial stages of Env activation: CD4 binding induces structural ordering throughout gp120 while loosening its association with gp41. The results indicate that uncleaved gp140 oligomers do not represent an authentic prefusion form of Env, whereas gp140 monomers isolated from the same glycoprotein preparations in many ways exhibit function and internal structural order that are consistent with expectations for certain aspects of native Env. gp140 monomers may thus be a useful reagent for advancing structural and functional studies.

Indexed as

Virus InternalizationCD4 Antigensenv Gene Products, Human Immunodeficiency VirusHIV-1HIV Envelope Protein gp120HIV Envelope Protein gp41Mass SpectrometryModels, MolecularProtein BindingProtein ConformationScattering, Small AngleCD4 Antigensenv Gene Products, Human Immunodeficiency Virusgp120 protein, Human immunodeficiency virus 1gp140 envelope protein, Human immunodeficiency virus 1gp41 protein, Human immunodeficiency virus 1HIV Envelope Protein gp120HIV Envelope Protein gp41

Identifiers

PMID23966389
PMCPMC3807357
OpenAlexW2164452020

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.