Evidence map›Paper›PMID 22733780›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Mapping the HLA-DO/HLA-DM complex by FRET and mutagenesis.

Taejin Yoon, Henriette Macmillan, Sarah E Mortimer, Wei Jiang, Cornelia H Rinderknecht, Lawrence J Stern, Elizabeth D Mellins

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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
2.0field-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

29 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Tuning DO:DM Ratios Modulates MHC Class II Immunopeptidomes.Molecular & cellular proteomics : MCP · 2022
    Article
  3. Review
  4. MHC Class II Presentation Is Affected by Polymorphism in theJournal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. HLA-DO Modulates the Diversity of the MHC-II Self-peptidome.Molecular & cellular proteomics : MCP · 2019
    Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. The MHC class II cofactor HLA-DM interacts with Ig in B cells.Journal of immunology (Baltimore, Md. : 1950) · 2014
    Article
  18. Review
  19. Article
  20. Review
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

7 authors at 2 institutions in 1 country.

Taejin YoonDepartment of Pediatrics, Program in Immunology, Stanford University, Stanford, CA 94305, USA.
Henriette Macmillan
Sarah E Mortimer
Wei Jiang
Cornelia H Rinderknecht
Lawrence J Stern
Elizabeth D Mellins
Stanford University · USUniversity of Massachusetts Chan Medical School · US

Funding

Spectrum Stanford Center for clinical and Translational Research and EducationUL1TR001085 · NCATS · STANFORD UNIVERSITY · PI CULLEN, MARK RICHARD, GREENBERG, HARRY BERNARD · 2013 to 2017
$37.1M
MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1UL1RR025744 · NCRR · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 2008 to 2011
$22.4M
TRAINING IN IMMUNOLOGY (COMPETITIVE RENEWAL OF AI07439)T32AI007349 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STERN, LAWRENCE J. · 1989 to 2024
$4.5M
Structure and Function of MHC ProteinsR37AI038996 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STERN, LAWRENCE J. · 2008 to 2017
$4.1M
Structure and Function of Class II MHC ProteinsR01AI038996 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STERN, LAWRENCE J · 1996 to 2006
$1.6M
Immunoglobulin as a novel ligand for HLA-DMR21AI095813 · NIAID · STANFORD UNIVERSITY · PI MELLINS, ELIZABETH D · 2011 to 2012
$435k
Structure and Function of Class II MHC ProteinsR56AI038996 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STERN, LAWRENCE J · 2007 to 2007
$324k
Kinetic and Structural Investigation of the Mechanism of Action of HLA-DOF32AI072984 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MORTIMER, SARAH E · 2007 to 2007
$47k
NCATS NIH HHS UL1 TR001085NCRR NIH HHS UL1 RR025744NIAID NIH HHS AI-095813NIAID NIH HHS AI-38996NIAID NIH HHS F32 AI072984NIAID NIH HHS R01 AI038996NIAID NIH HHS R21 AI095813NIAID NIH HHS R37 AI038996NIAID NIH HHS R56 AI038996NIAID NIH HHS T32 AI007290NIAID NIH HHS T32 AI007349NIAID NIH HHS T32 AI07290NIAID NIH HHS T32 AI07349
6 · The paper itself

Abstract

HLA-DO (DO) is a nonclassic class II heterodimer that inhibits the action of the class II peptide exchange catalyst, HLA-DM (DM), and influences DM localization within late endosomes and exosomes. In addition, DM acts as a chaperone for DO and is required for its egress from the endoplasmic reticulum (ER). These reciprocal functions are based on direct DO/DM binding, but the topology of DO/DM complexes is not known, in part, because of technical limitations stemming from DO instability. We generated two variants of recombinant soluble DO with increased stability [zippered DOαP11A (szDOv) and chimeric sDO-Fc] and confirmed their conformational integrity and ability to inhibit DM. Notably, we found that our constructs, as well as wild-type sDO, are inhibitory in the full pH range where DM is active (4.7 to ∼6.0). To probe the nature of DO/DM complexes, we used intermolecular fluorescence resonance energy transfer (FRET) and mutagenesis and identified a lateral surface spanning the α1 and α2 domains of szDO as the apparent binding site for sDM. We also analyzed several sDM mutants for binding to szDOv and susceptibility to DO inhibition. Results of these assays identified a region of DM important for interaction with DO. Collectively, our data define a putative binding surface and an overall orientation of the szDOv/sDM complex and have implications for the mechanism of DO inhibition of DM.

Indexed as

MutagenesisAnimalsAntigen PresentationAntigensBinding SitesEndoplasmic ReticulumFluorescence Resonance Energy TransferHLA-D AntigensHumansHydrogen-Ion ConcentrationMiceModels, MolecularPeptidesPolysaccharidesRecombinant ProteinsStatic ElectricityAntigensHLA-D AntigensHLA-DM antigensHLA-DO antigensPeptidesPolysaccharidesRecombinant Proteins

Identifiers

PMID22733780
PMCPMC3396517
OpenAlexW2150519497

What OpenQuestion holds

Textmetadata
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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.