Evidence map›Paper›PMID 25687963›Full record

ArticleJournal of molecular biology2016

The PRE-Derived NMR Model of the 38.8-kDa Tri-Domain IsdH Protein from Staphylococcus aureus Suggests That It Adaptively Recognizes Human Hemoglobin.

Megan Sjodt, Ramsay Macdonald, Thomas Spirig, Albert H Chan, Claire F Dickson, Marian Fabian, John S Olson, David A Gell, Robert T Clubb

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

Article in Journal of molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Cryo-EM provides insight into how thebioRxiv : the preprint server for biology · 2026
    Article
  2. Hemoglobin receptor redundancy inJournal of structural biology: X · 2025
    Article
  3. Article
  4. Article
  5. Cryo-EM structures of staphylococcal IsdB bound to human hemoglobin reveal the process of heme extraction.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  6. Article
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  8. Review
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  11. TheThe Journal of biological chemistry · 2018
    Article
  12. Energetics underlying hemin extraction from human hemoglobin byThe Journal of biological chemistry · 2018
    Article
  13. Article
  14. Article
  15. Article
  16. 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

9 authors at 3 institutions in 2 countries.

Megan SjodtDepartment of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; University of California, Los Angeles-Department of Energy Institute of Genomics and Proteomics, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
Ramsay MacdonaldDepartment of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; University of California, Los Angeles-Department of Energy Institute of Genomics and Proteomics, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
Thomas SpirigDepartment of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
Albert H ChanDepartment of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; University of California, Los Angeles-Department of Energy Institute of Genomics and Proteomics, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
Claire F DicksonMenzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania 7000, Australia.
Marian FabianDepartment of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA.
John S OlsonDepartment of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA.
David A GellMenzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania 7000, Australia.
Robert T ClubbDepartment of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; University of California, Los Angeles-Department of Energy Institute of Genomics and Proteomics, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA. Electronic address: rclubb@mbi.ucla.edu.
University of California, Los Angeles · USRice University · USUniversity of Tasmania · AU

Funding

UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
Recombinant HbAp Production for In Vivo Toxicity StudiesP01HL110900 · NHLBI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI ALAYASH, ABDU I. · 2012 to 2016
$10.6M
Cell Surface Protein Anchoring in Gram-Positive BacteriaR01AI052217 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Thompson Clubb · 2002 to 2026
$8.5M
BRUKER 800 MHZ TCI CRYOPROBE: STRUCTURES AND DYNAMICS OF PROTEINSS10RR022471 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CLUBB, ROBERT THOMPSON · 2006 to 2006
$301k
Hemoglobin Capture and Heme Acquisition by the Pathogen Staphylococcus AureusF31GM101931 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SJODT, MEGAN MARIE · 2012 to 2016
$158k
ITC: Isothermal Titration CalorimeterS10OD011994 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CLUBB, ROBERT THOMPSON · 2012 to 2012
$136k
NCRR NIH HHS S10 RR022471NHLBI NIH HHS P01 HL110900NHLBI NIH HHS P01-HL110900NIAID NIH HHS AI52217NIAID NIH HHS R01 AI052217NIGMS NIH HHS F31 GM101931NIGMS NIH HHS F31GM101931NIGMS NIH HHS T32 GM007185NIH HHS S10 OD011994
6 · The paper itself

Abstract

Staphylococcus aureus is a medically important bacterial pathogen that, during infections, acquires iron from human hemoglobin (Hb). It uses two closely related iron-regulated surface determinant (Isd) proteins to capture and extract the oxidized form of heme (hemin) from Hb, IsdH and IsdB. Both receptors rapidly extract hemin using a conserved tri-domain unit consisting of two NEAT (near iron transporter) domains connected by a helical linker domain. To gain insight into the mechanism of extraction, we used NMR to investigate the structure and dynamics of the 38.8-kDa tri-domain IsdH protein (IsdH(N2N3), A326-D660 with a Y642A mutation that prevents hemin binding). The structure was modeled using long-range paramagnetic relaxation enhancement (PRE) distance restraints, dihedral angle, small-angle X-ray scattering, residual dipolar coupling and inter-domain NOE nuclear Overhauser effect data. The receptor adopts an extended conformation wherein the linker and N3 domains pack against each other via a hydrophobic interface. In contrast, the N2 domain contacts the linker domain via a hydrophilic interface and, based on NMR relaxation data, undergoes inter-domain motions enabling it to reorient with respect to the body of the protein. Ensemble calculations were used to estimate the range of N2 domain positions compatible with the PRE data. A comparison of the Hb-free and Hb-bound forms reveals that Hb binding alters the positioning of the N2 domain. We propose that binding occurs through a combination of conformational selection and induced-fit mechanisms that may promote hemin release from Hb by altering the position of its F helix.

Indexed as

Antigens, BacterialHemoglobinsHumansMagnetic Resonance SpectroscopyModels, MolecularProtein BindingProtein ConformationReceptors, Cell SurfaceStaphylococcus aureusAntigens, BacterialHemoglobinsIsdH protein, Staphylococcus aureusReceptors, Cell Surfacehemoglobin receptoriron-regulated surface determinant systemlarge protein NMRnuclear magnetic resonance spectroscopyparamagnetic relaxation enhancement

Identifiers

PMID25687963
PMCPMC4537403
OpenAlexW2007961044

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Registered trials

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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.