Evidence map›Paper›PMID 35533763›Full record

ArticleJournal of molecular biology2022

Directed Inter-domain Motions Enable the IsdH Staphylococcus aureus Receptor to Rapidly Extract Heme from Human Hemoglobin.

Joseph Clayton, Kat Ellis-Guardiola, Brendan J Mahoney, Jess Soule, William Liu, Robert T Clubb, Jeff Wereszczynski

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

Article in Journal of molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

5 citing papers in PubMed, 7 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. Molecular basis of hemoglobin binding and heme removal inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Review
  5. The Shr receptor fromProceedings of the National Academy of Sciences of the United States of America · 2023
    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

7 authors at 2 institutions in 1 country.

Joseph ClaytonDepartment of Physics and Center for Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago, IL 60616, USA.
Kat Ellis-GuardiolaUCLA Department of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
Brendan J MahoneyUCLA Department of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
Jess SouleUCLA Department of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA; UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
William LiuUCLA Department of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
Robert T ClubbUCLA Department of Chemistry and Biochemistry, 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.
Jeff WereszczynskiDepartment of Physics and Center for Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago, IL 60616, USA. Electronic address: jweresz@iit.edu.
University of California, Los Angeles · USIllinois Institute of Technology · US

Funding

Cell Surface Protein Anchoring in Gram-Positive BacteriaR01AI052217 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Thompson Clubb · 2002 to 2026
$8.5M
Probing the Structure/Function/Dynamics Relationship in Biomolecular Complexes With Multiscale Computational TechniquesR35GM119647 · NIGMS · ILLINOIS INSTITUTE OF TECHNOLOGY · PI WERESZCZYNSKI, JEFFERY · 2016 to 2025
$3.8M
Molecular basis of heme scavenging by Gram-positive bacteriaR01AI161828 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Thompson Clubb · 2021 to 2026
$3.0M
Chemistry Biology Interface Training ProgramT32GM136614 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Patrick G. Harran · 2020 to 2026
$2.8M
800 MHz NMR Console and Cryoprobe ReplacementS10OD025073 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FEIGON, JULI · 2018 to 2018
$1.1M
Bruker Avance III Console and QCI Cryoprobe for a 600 MHz NMR SpectrometerS10OD016336 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CLUBB, ROBERT THOMPSON · 2014 to 2014
$600k
NIAID NIH HHS R01 AI052217NIAID NIH HHS R01 AI161828NIGMS NIH HHS R35 GM119647NIGMS NIH HHS T32 GM136614NIH HHS S10 OD016336NIH HHS S10 OD025073
6 · The paper itself

Abstract

Pathogenic Staphylococcus aureus actively acquires iron from human hemoglobin (Hb) using the IsdH surface receptor. Heme extraction is mediated by a tri-domain unit within the receptor that contains its second (N2) and third (N3) NEAT domains joined by a helical linker domain. Extraction occurs within a dynamic complex, in which receptors engage each globin chain; the N2 domain tightly binds to Hb, while substantial inter-domain motions within the receptor enable its N3 domain to transiently distort the globin's heme pocket. Using molecular simulations coupled with Markov modeling, along with stopped-flow experiments to quantitatively measure heme transfer kinetics, we show that directed inter-domain motions within the receptor play a critical role in the extraction process. The directionality of N3 domain motion and the rate of heme extraction is controlled by amino acids within a short, flexible inter-domain tether that connects the N2 and linker domains. In the wild-type receptor directed motions originating from the tether enable the N3 domain to populate configurations capable of distorting Hb's pocket, whereas mutant receptors containing altered tethers are less able to adopt these conformers and capture heme slowly via indirect processes in which Hb first releases heme into the solvent. Thus, our results show inter-domain motions within the IsdH receptor play a critical role in its ability to extract heme from Hb and highlight the importance of directed motions by the short, unstructured, amino acid sequence connecting the domains in controlling the directionality and magnitude of these functionally important motions.

Indexed as

Antigens, BacterialHemeHemoglobinsReceptors, Cell SurfaceStaphylococcal InfectionsStaphylococcus aureusHumansMolecular Dynamics SimulationMotionProtein DomainsAntigens, BacterialHemeHemoglobinsIsdH protein, Staphylococcus aureusReceptors, Cell Surfacehemoglobin receptoriron-regulated surface determinant systemmolecular dynamicsStaphylococcus aureusstopped-flow spectrophotometry

Identifiers

PMID35533763
PMCPMC9326902
OpenAlexW4229044168

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.