Evidence map›Paper›PMID 25525248›Full record

ArticleScience (New York, N.Y.)2014

De novo design of a transmembrane Zn²⁺-transporting four-helix bundle.

Nathan H Joh, Tuo Wang, Manasi P Bhate, Rudresh Acharya, Yibing Wu, Michael Grabe, Mei Hong, Gevorg Grigoryan, William F DeGrado

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.

0numbers the graph read from it
0cells of the map it votes in
160citing 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

160 citing papers in PubMed.

  1. Article
  2. Article
  3. bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  8. Review
  9. Designability of α-Helical Protein Filaments.Sub-cellular biochemistry · 2026
    Review
  10. Antibody Affinity Maturation by Computational Design.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. A Designed ZnJournal of the American Chemical Society · 2025
    Article
  17. Review
  18. Article
  19. Article
  20. Article

100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Nathan H JohDepartment of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Tuo WangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Manasi P BhateDepartment of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Rudresh AcharyaSchool of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, Odisha, India.
Yibing WuDepartment of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Michael GrabeDepartment of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA. william.degrado@ucsf.edu gevorg.grigoryan@dartmouth.edu meihong@mit.edu michael.grabe@ucsf.edu.
Mei HongDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. william.degrado@ucsf.edu gevorg.grigoryan@dartmouth.edu meihong@mit.edu michael.grabe@ucsf.edu.
Gevorg GrigoryanDepartment of Computer Science and Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA. william.degrado@ucsf.edu gevorg.grigoryan@dartmouth.edu meihong@mit.edu michael.grabe@ucsf.edu.
William F DeGradoDepartment of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA. william.degrado@ucsf.edu gevorg.grigoryan@dartmouth.edu meihong@mit.edu michael.grabe@ucsf.edu.

Funding

Structures and Dynamics of Proton and Cation-Dependent Channels and TransportersR01GM088204 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HONG, MEI · 2009 to 2024
$4.8M
Computational Studies of Sodium SymportersR01GM089740 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRABE, MICHAEL · 2011 to 2020
$2.8M
DE NOVO DESIGN OF ALPHA HELICAL BUNDLESR01GM054616 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI DEGRADO, WILLIAM · 1996 to 2016
$2.4M
Deciphering the Mechanism of Transporters by Design and ExperimentsF32GM096727 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI JOH, NATHAN · 2011 to 2013
$128k
NIGMS NIH HHS F32 GM096727NIGMS NIH HHS R01 GM054616NIGMS NIH HHS R01 GM088204NIGMS NIH HHS R01 GM089740
6 · The paper itself

Abstract

The design of functional membrane proteins from first principles represents a grand challenge in chemistry and structural biology. Here, we report the design of a membrane-spanning, four-helical bundle that transports first-row transition metal ions Zn(2+) and Co(2+), but not Ca(2+), across membranes. The conduction path was designed to contain two di-metal binding sites that bind with negative cooperativity. X-ray crystallography and solid-state and solution nuclear magnetic resonance indicate that the overall helical bundle is formed from two tightly interacting pairs of helices, which form individual domains that interact weakly along a more dynamic interface. Vesicle flux experiments show that as Zn(2+) ions diffuse down their concentration gradients, protons are antiported. These experiments illustrate the feasibility of designing membrane proteins with predefined structural and dynamic properties.

Indexed as

Protein EngineeringCarrier ProteinsCrystallography, X-RayIon TransportLipid BilayersMembrane ProteinsMicellesMolecular Dynamics SimulationProtein Structure, SecondaryZincCarrier ProteinsLipid BilayersMembrane ProteinsMicellesZinczinc-binding protein

Identifiers

PMID25525248
PMCPMC4400864

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.