Evidence map›Paper›PMID 26675729›Full record

ArticleNature2015

Exploring the repeat protein universe through computational protein design.

T J Brunette, Fabio Parmeggiani, Po-Ssu Huang, Gira Bhabha, Damian C Ekiert, Susan E Tsutakawa, Greg L Hura, John A Tainer, David Baker

Abstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.

0numbers the graph read from it
0cells of the map it votes in
150citing 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

150 citing papers in PubMed.

  1. Article
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  5. Article
  6. bioRxiv : the preprint server for biology · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Designability of α-Helical Protein Filaments.Sub-cellular biochemistry · 2026
    Review
  12. Article
  13. Article
  14. Article
  15. De novo design of metal-oxide templating proteins.bioRxiv : the preprint server for biology · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

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

9 authors.

T J BrunetteDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Fabio ParmeggianiDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Po-Ssu HuangDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Gira BhabhaDepartment of Cellular and Molecular Pharmacology, UCSF, San Francisco, California 94158, USA.
Damian C EkiertDepartment of Microbiology and Immunology, UCSF, San Francisco, California 94158, USA.
Susan E TsutakawaMolecular Biophysics &Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Greg L HuraMolecular Biophysics &Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
John A TainerMolecular Biophysics &Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.

Funding

THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI WIJSMAN, ELLEN M · 1985 to 2019
$57.2M
MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)R01GM105404 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI TAINER, JOHN A. · 2012 to 2015
$2.1M
Structure and mechanism of cytoplasmic and axonemal dyneinsK99GM112982 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BHABHA, GIRA · 2015 to 2016
$180k
Howard Hughes Medical InstituteNIA NIH HHS P50 AG005136NIGMS NIH HHS GM105404NIGMS NIH HHS K99 GM112982NIGMS NIH HHS K99GM112982NIGMS NIH HHS R01 GM105404
6 · The paper itself

Abstract

A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.

Indexed as

Amino Acid MotifsBioengineeringComputer SimulationProtein ConformationAmino Acid SequenceCrystallography, X-RayModels, MolecularProtein FoldingProteinsProtein StabilityTemperatureProteins

Identifiers

PMID26675729
PMCPMC4845728

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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.