Evidence map›Paper›PMID 26134567›Full record

ArticleThe Journal of biological chemistry2015

Heat Shock Protein 90 Associates with the Per-Arnt-Sim Domain of Heme-free Soluble Guanylate Cyclase: IMplications for Enzyme Maturation.

Anindya Sarkar, Yue Dai, Mohammad Mahfuzul Haque, Franziska Seeger, Arnab Ghosh, Elsa D Garcin, William R Montfort, Stanley L Hazen, Saurav Misra, Dennis J Stuehr

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Key roles of GAPDH, Hsp90, and NO in heme trafficking.Journal of inorganic biochemistry · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. GAPDH delivers heme to soluble guanylyl cyclase.The Journal of biological chemistry · 2020
    Article
  12. Myoglobin maturation is driven by the hsp90 chaperone machinery and by soluble guanylyl cyclase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Hsp90 chaperones hemoglobin maturation in erythroid and nonerythroid cells.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  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

10 authors at 3 institutions in 1 country.

Anindya SarkarFrom the Departments of Pathobiology.
Yue DaiFrom the Departments of Pathobiology.
Mohammad Mahfuzul HaqueFrom the Departments of Pathobiology.
Franziska Seegerthe Department of Chemistry and Biochemistry, University of Maryland at Baltimore County, Baltimore, Maryland 21250, and.
Arnab GhoshFrom the Departments of Pathobiology.
Elsa D Garcinthe Department of Chemistry and Biochemistry, University of Maryland at Baltimore County, Baltimore, Maryland 21250, and.
William R Montfortthe Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721.
Stanley L HazenCellular and Molecular Medicine, and.
Saurav MisraMolecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195.
Dennis J StuehrFrom the Departments of Pathobiology, stuehrd@ccf.org.
Cleveland Clinic Lerner College of Medicine · USUniversity of Maryland, Baltimore County · USUniversity of Arizona · US

Funding

Structural Determinants Of Ceruloplasmin Inflammatory ActivityP01HL076491 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PLOW, EDWARD FRANKLIN · 2004 to 2019
$27.3M
CONTROL MECHANISMS OF THE NITRIC OXIDE SYNTHASESR01GM051491 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI STUEHR, DENNIS J · 1994 to 2016
$5.1M
SALIVARY PROTEINS FROM BLOOD-SUCKING INSECTSR01HL062969 · NHLBI · UNIVERSITY OF ARIZONA · PI MONTFORT, WILLIAM R. · 2000 to 2012
$3.4M
New mechanism and regulation of intracellular heme delivery in mammalsR01GM097041 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI STUEHR, DENNIS J · 2011 to 2014
$1.2M
NHLBI NIH HHS HL076491NHLBI NIH HHS P01 HL076491NHLBI NIH HHS R01 HL062969NIGMS NIH HHS GM051491NIGMS NIH HHS GM097041NIGMS NIH HHS R01 GM051491NIGMS NIH HHS R01 GM097041
6 · The paper itself

Abstract

Heat shock protein 90 (hsp90) drives heme insertion into the β1 subunit of soluble guanylate cyclase (sGC) β1, which enables it to associate with a partner sGCα1 subunit and mature into a nitric oxide (NO)-responsive active form. We utilized fluorescence polarization measurements and hydrogen-deuterium exchange mass spectrometry to define molecular interactions between the specific human isoforms hsp90β and apo-sGCβ1. hsp90β and its isolated M domain, but not its isolated N and C domains, bind with low micromolar affinity to a heme-free, truncated version of sGCβ1 (sGCβ1(1-359)-H105F). Surprisingly, hsp90β and its M domain bound to the Per-Arnt-Sim (PAS) domain of apo-sGC-β1(1-359), which lies adjacent to its heme-binding (H-NOX) domain. The interaction specifically involved solvent-exposed regions in the hsp90β M domain that are largely distinct from sites utilized by other hsp90 clients. The interaction strongly protected two regions of the sGCβ1 PAS domain and caused local structural relaxation in other regions, including a PAS dimerization interface and a segment in the H-NOX domain. Our results suggest a means by which the hsp90β interaction could prevent apo-sGCβ1 from associating with its partner sGCα1 subunit while enabling structural changes to assist heme insertion into the H-NOX domain. This mechanism would parallel that in other clients like the aryl hydrocarbon receptor and HIF1α, which also interact with hsp90 through their PAS domains to control protein partner and small ligand binding interactions.

Indexed as

Amino Acid SequenceAnimalsCattleDeuterium Exchange MeasurementGuanylate CyclaseHemeHSP90 Heat-Shock ProteinsHumansKineticsModels, MolecularMolecular Sequence DataProtein BindingProtein Structure, TertiaryReceptors, Cytoplasmic and NuclearSoluble Guanylyl CyclaseGuanylate CyclaseHemeHSP90 Heat-Shock ProteinsReceptors, Cytoplasmic and NuclearSoluble Guanylyl Cyclasecyclic GMP (cGMP)fluorescence anisotropyheat shock protein 90 (hsp90)heme insertionH-NOX domainhydrogen exchange mass spectrometryPAS domainprotein-protein interactionsignal transductionstructural modeling

Identifiers

PMID26134567
PMCPMC4571885
OpenAlexW2285009903

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.