Evidence map›Paper›PMID 33972753›Full record

ArticleNature chemistry2021

Constructing ion channels from water-soluble α-helical barrels.

Alistair J Scott, Ai Niitsu, Huong T Kratochvil, Eric J M Lang, Jason T Sengel, William M Dawson, Kozhinjampara R Mahendran, Marco Mravic, Andrew R Thomson, R Leo Brady and 6 more

Open access · greenAbstract read
In one paragraph

Article in Nature chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

60 citing papers in PubMed, 117 citations in OpenAlex.

  1. Article
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  3. Sculpting semisynthetic conducting protein pores by de novo design.Nature structural & molecular biology · 2026
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  4. De novo design of semisynthetic conduction pores.Nature structural & molecular biology · 2026
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  6. bioRxiv : the preprint server for biology · 2026
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  9. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  10. Exploring the Blueprint of Life: The Innovation in Antibody and Protein Design.Combinatorial chemistry & high throughput screening · 2026
    Article
  11. Designability of α-Helical Protein Filaments.Sub-cellular biochemistry · 2026
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Design principles of the common Gly-X6-Gly membrane protein building block.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 4 countries.

Alistair J Scott *School of Chemistry, University of Bristol, Bristol, UK.
Ai Niitsu *School of Chemistry, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-7823-9041
Huong T KratochvilDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Eric J M LangSchool of Chemistry, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-3808-054X
Jason T SengelDepartment of Chemistry, King's College London, London, UK.
William M DawsonSchool of Chemistry, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0003-2710-6879
Kozhinjampara R MahendranDepartment of Chemistry, University of Oxford, Oxford, UK.
Marco MravicDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Andrew R ThomsonSchool of Chemistry, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-1066-1369
R Leo BradySchool of Biochemistry, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-3575-5513
Lijun LiuSchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, People's Republic of China.ORCID http://orcid.org/0000-0003-0514-281X
Adrian J MulhollandSchool of Chemistry, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0003-1015-4567
Hagan BayleyDepartment of Chemistry, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-2499-6116
William F DeGradoDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Mark I WallaceDepartment of Chemistry, King's College London, London, UK.ORCID http://orcid.org/0000-0002-5692-8313
Derek N WoolfsonSchool of Chemistry, University of Bristol, Bristol, UK. d.n.woolfson@bristol.ac.uk.ORCID http://orcid.org/0000-0002-0394-3202
University of Bristol · GBUniversity of California, San Francisco · USKing's College London · GBUniversity of Oxford · GBPeking University · CNPioneer (United States) · US

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI James M Holton · 2017 to 2026
$28.6M
STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1M
Deciphering the relationship between structure, dynamics and function in helical bundle proteinsR35GM122603 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WILLIAM DEGRADO · 2017 to 2026
$7.1M
Eliminating Critical Systematic Errors In Structural Biology With Next-Generation SimulationR01GM124149 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HOLTON, JAMES M · 2017 to 2024
$2.5M
A structural and biophysical study of the matrix proteins in influenza A/B viruses: Mechanisms of proton conduction and roles of protein-protein interactionsF32GM125217 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRATOCHVIL, HUONG TRAN · 2017 to 2019
$177k
Biotechnology and Biological Sciences Research Council BB/J009784/1Biotechnology and Biological Sciences Research Council BB/L01386X/1Biotechnology and Biological Sciences Research Council BB/R001790/1European Research Council 340764Howard Hughes Medical Institute (HHMI) NANIGMS NIH HHS F32 GM125217NIGMS NIH HHS P30 GM124169NIGMS NIH HHS R01 GM124149NIGMS NIH HHS R35 GM122603NIGMS NIH HHS T32 GM008284
6 · The paper itself

Abstract

The design of peptides that assemble in membranes to form functional ion channels is challenging. Specifically, hydrophobic interactions must be designed between the peptides and at the peptide-lipid interfaces simultaneously. Here, we take a multi-step approach towards this problem. First, we use rational de novo design to generate water-soluble α-helical barrels with polar interiors, and confirm their structures using high-resolution X-ray crystallography. These α-helical barrels have water-filled lumens like those of transmembrane channels. Next, we modify the sequences to facilitate their insertion into lipid bilayers. Single-channel electrical recordings and fluorescent imaging of the peptides in membranes show monodisperse, cation-selective channels of unitary conductance. Surprisingly, however, an X-ray structure solved from the lipidic cubic phase for one peptide reveals an alternative state with tightly packed helices and a constricted channel. To reconcile these observations, we perform computational analyses to compare the properties of possible different states of the peptide.

Indexed as

Amino Acid SequenceIon ChannelsLipid BilayersMolecular Dynamics SimulationPeptidesProtein Conformation, alpha-HelicalProtein EngineeringSolubilityWaterIon ChannelsLipid BilayersPeptidesWater

Identifiers

PMID33972753
PMCPMC7611114
OpenAlexW3161348944

What OpenQuestion holds

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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.