Evidence map›Paper›PMID 26027734›Full record

ArticleStructure (London, England : 1993)2015

Structural Basis for Modulation of Quality Control Fate in a Marginally Stable Protein.

Kelly P Brock, Ayelet-chen Abraham, Triana Amen, Daniel Kaganovich, Jeremy L England

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Imaging stress.Cell stress & chaperones · 2015
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Kelly P BrockComputational and Systems Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Ayelet-chen AbrahamDepartment of Cell and Developmental Biology, Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
Triana AmenDepartment of Cell and Developmental Biology, Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel; Alexander Grass Center for Bioengineering, Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
Daniel KaganovichDepartment of Cell and Developmental Biology, Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel. Electronic address: dan@cc.huji.ac.il.
Jeremy L EnglandPhysics of Living Systems Group, Department of Physics, Massachusetts Institute of Technology, 400 Tech Square, Cambridge, MA 02139, USA. Electronic address: jengland@mit.edu.
Hebrew University of Jerusalem · ILLiving Systems (United States) · USMassachusetts Institute of Technology · US

Funding

Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
NIGMS NIH HHS T32 GM087237
6 · The paper itself

Abstract

The human von Hippel-Lindau (VHL) tumor suppressor is a marginally stable protein previously used as a model substrate of eukaryotic refolding and degradation pathways. When expressed in the absence of its cofactors, VHL cannot fold and is quickly degraded by the quality control machinery of the cell. We combined computational methods with in vivo experiments to examine the basis of the misfolding propensity of VHL. By expressing a set of randomly mutated VHL sequences in yeast, we discovered a more stable mutant form. Subsequent modeling suggested the mutation had caused a conformational change affecting cofactor and chaperone interaction, and this hypothesis was then confirmed by additional knockout and overexpression experiments targeting a yeast cofactor homolog. These findings offer a detailed structural basis for the modulation of quality control fate in a model misfolded protein and highlight burial mode modeling as a rapid means to detect functionally important conformational changes in marginally stable globular domains.

Indexed as

Amino Acid SequenceAmino Acid SubstitutionEnzyme StabilityHumansModels, MolecularMolecular Sequence DataSaccharomyces cerevisiaeVon Hippel-Lindau Tumor Suppressor ProteinVHL protein, humanVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID26027734
PMCPMC4509718
OpenAlexW1559034308

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.