Evidence map›Paper›PMID 12631739›Full record

ArticleMolecular biology of the cell2003

Recognition of a single transmembrane degron by sequential quality control checkpoints.

Laurence Fayadat, Ron R Kopito

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  6. Article
  7. Protein homeostasis at the plasma membrane.Physiology (Bethesda, Md.) · 2014
    Review
  8. Article
  9. Protein quality control at the plasma membrane.Current opinion in cell biology · 2011
    Review
  10. Article
  11. Article
  12. Article
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  15. Article
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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.

Laurence FayadatDepartment of Biological Sciences, Stanford University, California 94305-5020, USA.
Ron R Kopito
Stanford University · US

Funding

MOLECULAR AND CELLULAR BIOLOGY OF THE CFTRR01DK043994 · NIDDK · STANFORD UNIVERSITY · PI KOPITO, RON R · 1991 to 2003
$873k
NIDDK NIH HHS DK43994NIDDK NIH HHS R01 DK043994
6 · The paper itself

Abstract

To understand the relationship between conformational maturation and quality control-mediated proteolysis in the secretory pathway, we engineered the well-characterized degron from the alpha-subunit of the T-cell antigen receptor (TCRalpha) into the alpha-helical transmembrane domain of homotrimeric type I integral membrane protein, influenza hemagglutinin (HA). Although the membrane degron does not appear to interfere with acquisition of native secondary structure, as assessed by the formation of native intrachain disulfide bonds, only approximately 50% of nascent mutant HA chains (HA(++)) become membrane-integrated and acquire complex N-linked glycans indicative of transit to a post-ER compartment. The remaining approximately 50% of nascent HA(++) chains fail to integrate into the lipid bilayer and are subject to proteasome-dependent degradation. Site-specific cleavage by extracellular trypsin and reactivity with conformation-specific monoclonal antibodies indicate that membrane-integrated HA(++) molecules are able to mature to the plasma membrane with a conformation indistinguishable from that of HA(wt). These apparently native HA(++) molecules are, nevertheless, rapidly degraded by a process that is insensitive to proteasome inhibitors but blocked by lysosomotropic amines. These data suggest the existence in the secretory pathway of at least two sequential quality control checkpoints that recognize the same transmembrane degron, thereby ensuring the fidelity of protein deployment to the plasma membrane.

Indexed as

Amino Acid SequenceProtein FoldingProtein Structure, SecondaryAnimalsCell LineCell MembraneCysteine EndopeptidasesDisulfidesExocytosisHemagglutinin Glycoproteins, Influenza VirusHumansLysosomesMembrane ProteinsMultienzyme ComplexesProteasome Endopeptidase ComplexProtein Structure, QuaternaryCysteine EndopeptidasesDisulfidesHemagglutinin Glycoproteins, Influenza VirusMembrane ProteinsMultienzyme ComplexesProteasome Endopeptidase ComplexReceptors, Antigen, T-Cell

Identifiers

PMID12631739
PMCPMC151595
OpenAlexW2137390014

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.