Evidence map›Paper›PMID 37095238›Full record

ArticleNature chemical biology2023

Dissecting the conformational complexity and mechanism of a bacterial heme transporter.

Di Wu, Ahmad R Mehdipour, Franziska Finke, Hojjat G Goojani, Roan R Groh, Tamara N Grund, Thomas M B Reichhart, Rita Zimmermann, Sonja Welsch, Dirk Bald and 3 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

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  14. Structural aspects of enzymes involved in prokaryotic Gram-positive heme biosynthesis.Computational and structural biotechnology journal · 2023
    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

13 authors.

Di WuDepartment of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt/Main, Germany.
Ahmad R MehdipourDepartment of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt/Main, Germany.
Franziska FinkeDepartment of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt/Main, Germany.
Hojjat G GoojaniAmsterdam Institute for Life and Environment (A-LIFE), AIMMS, Faculty of Science, Vrije University of Amsterdam, Amsterdam, the Netherlands.
Roan R GrohDepartment of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt/Main, Germany.
Tamara N GrundDepartment of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt/Main, Germany.
Thomas M B ReichhartDepartment of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt/Main, Germany.
Rita ZimmermannDepartment of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt/Main, Germany.
Sonja WelschCentral Electron Microscopy Facility, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.ORCID 0000-0002-6049-6664
Dirk BaldAmsterdam Institute for Life and Environment (A-LIFE), AIMMS, Faculty of Science, Vrije University of Amsterdam, Amsterdam, the Netherlands.
Mark ShepherdSchool of Biosciences, RAPID Group, University of Kent, Canterbury, UK.
Gerhard HummerDepartment of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt/Main, Germany.ORCID 0000-0001-7768-746X
Schara SafarianDepartment of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt/Main, Germany. schara.safarian@biophys.mpg.de.ORCID 0000-0002-0232-1612

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Iron-bound cyclic tetrapyrroles (hemes) are redox-active cofactors in bioenergetic enzymes. However, the mechanisms of heme transport and insertion into respiratory chain complexes remain unclear. Here, we used cellular, biochemical, structural and computational methods to characterize the structure and function of the heterodimeric bacterial ABC transporter CydDC. We provide multi-level evidence that CydDC is a heme transporter required for functional maturation of cytochrome bd, a pharmaceutically relevant drug target. Our systematic single-particle cryogenic-electron microscopy approach combined with atomistic molecular dynamics simulations provides detailed insight into the conformational landscape of CydDC during substrate binding and occlusion. Our simulations reveal that heme binds laterally from the membrane space to the transmembrane region of CydDC, enabled by a highly asymmetrical inward-facing CydDC conformation. During the binding process, heme propionates interact with positively charged residues on the surface and later in the substrate-binding pocket of the transporter, causing the heme orientation to rotate 180°.

Indexed as

Escherichia coli ProteinsHemeATP-Binding Cassette TransportersEscherichia coliOxidation-ReductionProtein ConformationATP-Binding Cassette TransportersEscherichia coli ProteinsHeme

Identifiers

PMID37095238
PMCPMC10374445

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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.