Evidence map›Paper›PMID 22542781›Full record

ArticleBiochimica et biophysica acta2012

Structural and biochemical studies of the open state of Lys48-linked diubiquitin.

Ming-Yih Lai, Daoning Zhang, Nicole Laronde-Leblanc, David Fushman

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Activated Protein C Ameliorates Diabetic CardiomyopathyFrontiers in cardiovascular medicine · 2021
    Article
  11. Article
  12. Article
  13. Article
  14. Ubiquitin S65 phosphorylation engenders a pH-sensitive conformational switch.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  15. Article
  16. Non-degradative Ubiquitination of Protein Kinases.PLoS computational biology · 2016
    Article
  17. Article
  18. Article
  19. 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 1 country.

Ming-Yih LaiDepartment of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
Daoning Zhang
Nicole Laronde-Leblanc
David Fushman
University of Maryland, College Park · US

Funding

Y-FAMILY POLYMERASES AND CO-FACTORS IN TRANSLESION REPLICATIONP41RR015301 · NCRR · CORNELL UNIVERSITY ITHACA · PI EISENBERG, DAVID · 2001 to 2011
$28.2M
Solution structure and dynamics of polyubiquitin chainsR01GM065334 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI DAVID FUSHMAN · 2002 to 2026
$6.2M
Recognition of non-ubiquitin signals at the proteasomeR01GM095755 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI FUSHMAN, DAVID · 2011 to 2014
$1.4M
NCRR NIH HHS P41 RR015301NCRR NIH HHS RR-15301NIGMS NIH HHS GM065334NIGMS NIH HHS GM095755NIGMS NIH HHS R01 GM065334NIGMS NIH HHS R01 GM095755
6 · The paper itself

Abstract

Ubiquitin (Ub) is a small protein highly conserved among eukaryotes and involved in practically all aspects of eukaryotic cell biology. Polymeric chains assembled from covalently-linked Ub monomers function as molecular signals in the regulation of a host of cellular processes. Our previous studies have shown that the predominant state of Lys48-linked di- and tetra-Ub chains at near-physiological conditions is a closed conformation, in which the Ub-Ub interface is formed by the hydrophobic surface residues of the adjacent Ub units. Because these very residues are involved in (poly)Ub interactions with the majority of Ub-binding proteins, their sequestration at the Ub-Ub interface renders the closed conformation of polyUb binding incompetent. Thus the existence of open conformation(s) and the interdomain motions opening and closing the Ub-Ub interface is critical for the recognition of Lys48-linked polyUb by its receptors. Knowledge of the conformational properties of a polyUb signal is essential for our understanding of its specific recognition by various Ub-receptors. Despite their functional importance, open states of Lys48-linked chains are poorly characterized. Here we report a crystal structure of the open state of Lys48-linked di-Ub. Moreover, using NMR, we examined interactions of the open state of this chain (at pH4.5) with a Lys48-linkage-selective receptor, the UBA2 domain of a shuttle protein hHR23a. Our results show that di-Ub binds UBA2 in the same mode and with comparable affinity as the closed state. Our data suggest a mechanism for polyUb signal recognition, whereby Ub-binding proteins select specific conformations out of the available ensemble of polyUb chain conformations. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.

Indexed as

Crystallography, X-RayDNA-Binding ProteinsDNA Repair EnzymesHumansLysineMagnetic Resonance SpectroscopyModels, MolecularPolyubiquitinProtein BindingProtein ConformationUbiquitin-Activating EnzymesDNA-Binding ProteinsDNA Repair EnzymesLysinePolyubiquitinRAD23A protein, humanUBA2 protein, humanUbiquitin-Activating Enzymes

Identifiers

PMID22542781
PMCPMC3429157
OpenAlexW2005345675

What OpenQuestion holds

Textmetadata
LicenceTDM
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.