Evidence map›Paper›PMID 28753126›Full record

ArticleeLife2017

Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide.

Erik Lee Snapp, Nicholas McCaul, Matthias Quandte, Zuzana Cabartova, Ilja Bontjer, Carolina Källgren, IngMarie Nilsson, Aafke Land, Gunnar von Heijne, Rogier W Sanders and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

35 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Structural insights into SARS-CoV-2 nonstructural protein 4 (nsp4) biogenesis.Protein science : a publication of the Protein Society · 2025
    Article
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  20. Differential genotypic signatures of Toll-like receptor polymorphisms among dengue-chikungunya mono- and co-infected Eastern Indian patients.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021
    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

11 authors at 5 institutions in 4 countries.

Erik Lee Snapp *Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Nicholas McCaul *Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Matthias QuandteCellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Zuzana CabartovaNational Institute of Public Health, National Reference Laboratory for Viral Hepatitis, Prague, Czech Republic.
Ilja BontjerDepartment of Medical Microbiology, Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, Netherlands.
Carolina KällgrenDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
IngMarie NilssonDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Aafke LandCellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Gunnar von HeijneDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.ORCID https://orcid.org/0000-0002-4490-8569
Rogier W SandersDepartment of Medical Microbiology, Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, Netherlands.
Ineke BraakmanCellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands.ORCID http://orcid.org/0000-0003-1592-4364
Utrecht University · NLStockholm University · SEAmsterdam UMC Location University of Amsterdam · NLHoward Hughes Medical Institute · USNational Institute of Public Health · CZ

Funding

Immunology/Pathology CoreP30AI051519 · NIAID · YESHIVA UNIVERSITY · PI GOLDSTEIN, HARRIS · 2003 to 2013
$18.6M
European Research Council 280829NIAID NIH HHS P30 AI051519
6 · The paper itself

Abstract

Like all other secretory proteins, the HIV-1 envelope glycoprotein gp160 is targeted to the endoplasmic reticulum (ER) by its signal peptide during synthesis. Proper gp160 folding in the ER requires core glycosylation, disulfide-bond formation and proline isomerization. Signal-peptide cleavage occurs only late after gp160 chain termination and is dependent on folding of the soluble subunit gp120 to a near-native conformation. We here detail the mechanism by which co-translational signal-peptide cleavage is prevented. Conserved residues from the signal peptide and residues downstream of the canonical cleavage site form an extended alpha-helix in the ER membrane, which covers the cleavage site, thus preventing cleavage. A point mutation in the signal peptide breaks the alpha helix allowing co-translational cleavage. We demonstrate that postponed cleavage of gp160 enhances functional folding of the molecule. The change to early cleavage results in decreased viral fitness compared to wild-type HIV.

Indexed as

Protein FoldingProtein Sorting SignalsCell LineHIV-1HIV Envelope Protein gp160HumansProtein ConformationProtein TransportProteolysisgp160 protein, Human immunodeficiency virus 1HIV Envelope Protein gp160Protein Sorting Signalsbiochemistrycell biologyendoplasmic reticulumgp160HIVhumanprotein foldingsignal peptidetranslocation

Identifiers

PMID28753126
PMCPMC5577925
OpenAlexW2741183908

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.