Evidence map›Paper›PMID 21543498›Full record

ArticleJournal of virology2011

The domain I-domain III linker plays an important role in the fusogenic conformational change of the alphavirus membrane fusion protein.

Yan Zheng, Claudia Sánchez-San Martín, Zhao-ling Qin, Margaret Kielian

Abstract read
In one paragraph

Article in Journal of virology, 2011. 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
4.1field-weighted citation impact, top 7% 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, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Entry receptors - the gateway to alphavirus infection.The Journal of clinical investigation · 2023
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Fusion of Enveloped Viruses in Endosomes.Traffic (Copenhagen, Denmark) · 2016
    Review
  16. Review
  17. Article
  18. Article
  19. Crystal structure of glycoprotein E2 from bovine viral diarrhea virus.Proceedings of the National Academy of Sciences of the United States of America · 2013
    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

4 authors at 1 institution in 2 countries.

Yan ZhengDepartment of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. margaret.kielian@einstein.yu.edu
Claudia Sánchez-San Martín
Zhao-ling Qin
Margaret Kielian
Albert Einstein College of Medicine · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2M
Molecular Analysis of Alphavirus Membrane Fusion ProteinR01AI075647 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI KIELIAN, MARGARET · 2007 to 2023
$9.0M
NCI NIH HHS P30 CA013330NCI NIH HHS P30-CA013330NIAID NIH HHS R01 AI075647NIAID NIH HHS R01-AI075647
6 · The paper itself

Abstract

The alphavirus Semliki Forest virus (SFV) infects cells through a low-pH-dependent membrane fusion reaction mediated by the virus fusion protein E1. Acidic pH initiates a series of E1 conformational changes that culminate in membrane fusion and include dissociation of the E1/E2 heterodimer, insertion of the E1 fusion loop into the target membrane, and refolding of E1 to a stable trimeric hairpin conformation. A highly conserved histidine (H3) on the E1 protein was previously shown to promote low-pH-dependent E1 refolding. An SFV mutant with an alanine substitution at this position (H3A) has a lower pH threshold and reduced efficiency of virus fusion and E1 trimer formation than wild-type SFV. Here we addressed the mechanism by which H3 promotes E1 refolding and membrane fusion. We identified E1 mutations that rescue the H3A defect. These revertants implicated a network of interactions that connect the domain I-domain III (DI-DIII) linker region with the E1 core trimer, including H3. In support of the importance of these interactions, mutation of residues in the network resulted in more acidic pH thresholds and reduced efficiencies of membrane fusion. In vitro studies of truncated E1 proteins demonstrated that the DI-DIII linker was required for production of a stable E1 core trimer on target membranes. Together, our results suggest a critical and previously unidentified role for the DI-DIII linker region during the low-pH-dependent refolding of E1 that drives membrane fusion.

Indexed as

Membrane FusionAlphavirusAnimalsCricetinaeHistidineHydrogen-Ion ConcentrationMembrane GlycoproteinsMutationProtein ConformationProtein FoldingProtein MultimerizationProtein Structure, TertiarySemliki forest virusViral Envelope ProteinsViral Fusion ProteinsE1 glycoprotein, Semliki forest virusHistidineMembrane GlycoproteinsViral Envelope ProteinsViral Fusion Proteins

Identifiers

PMID21543498
PMCPMC3126531
OpenAlexW2121056637

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.