Evidence map›Paper›PMID 31113958›Full record

ArticleNature communications2019

The extracellular gate shapes the energy profile of an ABC exporter.

Cedric A J Hutter, M Hadi Timachi, Lea M Hürlimann, Iwan Zimmermann, Pascal Egloff, Hendrik Göddeke, Svetlana Kucher, Saša Štefanić, Mikko Karttunen, Lars V Schäfer and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing 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

40 citing papers in PubMed.

  1. Article
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  6. The journal of physical chemistry. C, Nanomaterials and interfaces · 2025
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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

12 authors.

Cedric A J HutterInstitute of Medical Microbiology, University of Zurich, Gloriastr. 28/30, 8006, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-8920-3343
M Hadi TimachiFaculty of Chemistry and Biochemistry, Ruhr University Bochum, 44801, Bochum, Germany.
Lea M HürlimannInstitute of Medical Microbiology, University of Zurich, Gloriastr. 28/30, 8006, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-9907-7830
Iwan ZimmermannInstitute of Medical Microbiology, University of Zurich, Gloriastr. 28/30, 8006, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-3476-4749
Pascal EgloffInstitute of Medical Microbiology, University of Zurich, Gloriastr. 28/30, 8006, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-8948-3704
Hendrik GöddekeTheoretical Chemistry, Faculty of Chemistry and Biochemistry, Ruhr University Bochum, 44801, Bochum, Germany.
Svetlana KucherFaculty of Chemistry and Biochemistry, Ruhr University Bochum, 44801, Bochum, Germany.
Saša ŠtefanićInstitute of Parasitology, University of Zurich, Winterthurerstrasse 266a, 8057, Zurich, Switzerland.
Mikko KarttunenDepartment of Chemistry and Department of Applied Mathematics, The University of Western Ontario, London, ON, N6A 3K7, Canada.ORCID http://orcid.org/0000-0002-8626-3033
Lars V SchäferTheoretical Chemistry, Faculty of Chemistry and Biochemistry, Ruhr University Bochum, 44801, Bochum, Germany.ORCID http://orcid.org/0000-0002-8498-3061
Enrica BordignonFaculty of Chemistry and Biochemistry, Ruhr University Bochum, 44801, Bochum, Germany. enrica.bordignon@rub.de.
Markus A SeegerInstitute of Medical Microbiology, University of Zurich, Gloriastr. 28/30, 8006, Zurich, Switzerland. m.seeger@imm.uzh.ch.ORCID http://orcid.org/0000-0003-1761-8571

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ABC exporters harness the energy of ATP to pump substrates across membranes. Extracellular gate opening and closure are key steps of the transport cycle, but the underlying mechanism is poorly understood. Here, we generated a synthetic single domain antibody (sybody) that recognizes the heterodimeric ABC exporter TM287/288 exclusively in the presence of ATP, which was essential to solve a 3.2 Å crystal structure of the outward-facing transporter. The sybody binds to an extracellular wing and strongly inhibits ATPase activity by shifting the transporter's conformational equilibrium towards the outward-facing state, as shown by double electron-electron resonance (DEER). Mutations that facilitate extracellular gate opening result in a comparable equilibrium shift and strongly reduce ATPase activity and drug transport. Using the sybody as conformational probe, we demonstrate that efficient extracellular gate closure is required to dissociate the NBD dimer after ATP hydrolysis to reset the transporter back to its inward-facing state.

Indexed as

Molecular Dynamics SimulationAAA DomainATP-Binding Cassette TransportersBacterial ProteinsElectron Spin Resonance SpectroscopyMutationProtein MultimerizationSingle-Domain AntibodiesThermotoga maritimaATP-Binding Cassette TransportersBacterial ProteinsSingle-Domain Antibodies

Identifiers

PMID31113958
PMCPMC6529423

What OpenQuestion holds

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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.