Evidence map›Paper›PMID 38816644›Full record

ArticleNature chemical biology2024

De novo design of buttressed loops for sculpting protein functions.

Hanlun Jiang, Kevin M Jude, Kejia Wu, Jorge Fallas, George Ueda, T J Brunette, Derrick R Hicks, Harley Pyles, Aerin Yang, Lauren Carter and 6 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. De novo design of metal-oxide templating proteins.bioRxiv : the preprint server for biology · 2025
    Article
  6. AI4Protein: transforming the future of protein design.Science China. Life sciences · 2025
    Review
  7. Article
  8. Design and evolution of a synthetic small protein scaffold based on the WW domain.Protein science : a publication of the Protein Society · 2025
    Article
  9. A Foundational Shift in Models for Enzyme Function.Journal of the American Chemical Society · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Geometric descriptors for beta turns.Protein science : a publication of the Protein Society · 2024
    Article
  16. Article
4 · The record

Corrections and comments

  • Update of
    2023
5 · Who and what money

Authors and funding

16 authors.

Hanlun Jiang *Department of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-4649-1584
Kevin M Jude *Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3675-5136
Kejia Wu *Department of Biochemistry, University of Washington, Seattle, WA, USA.
Jorge FallasDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
George UedaDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9792-7149
T J BrunetteDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Derrick R HicksDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Harley PylesDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Aerin YangDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8704-0288
Lauren CarterDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Mila LambDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Xinting LiDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Paul M LevineDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Lance StewartDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-4264-5125
K Christopher GarciaHoward Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. kcgarcia@stanford.edu.ORCID http://orcid.org/0000-0001-9273-0278
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA, USA. dabaker@uw.edu.ORCID http://orcid.org/0000-0001-7896-6217

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Ritimukta Sarangi · 2020 to 2026
$43.3M
User Training & OutreachP30GM138396 · NIGMS · UCHICAGO ARGONNE, LLC · PI JANET L. SMITH · 2020 to 2026
$34.3M
High-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APSS10OD012289 · OD · UNIVERSITY OF CHICAGO · PI FISCHETTI, ROBERT F. · 2014 to 2014
$2.0M
DOE | LDRD | Argonne National Laboratory (ANL) DE-AC02-06CH11357DOE | SC | Basic Energy Sciences (BES) DE-AC02-76SF00515NIGMS NIH HHS P30 GM133894NIGMS NIH HHS P30 GM138396NIH HHS S10 OD012289ODCDC CDC HHS S10 OD012289U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) ACB-12002U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) P30GM133894
6 · The paper itself

Abstract

In natural proteins, structured loops have central roles in molecular recognition, signal transduction and enzyme catalysis. However, because of the intrinsic flexibility and irregularity of loop regions, organizing multiple structured loops at protein functional sites has been very difficult to achieve by de novo protein design. Here we describe a solution to this problem that designs tandem repeat proteins with structured loops (9-14 residues) buttressed by extensive hydrogen bonding interactions. Experimental characterization shows that the designs are monodisperse, highly soluble, folded and thermally stable. Crystal structures are in close agreement with the design models, with the loops structured and buttressed as designed. We demonstrate the functionality afforded by loop buttressing by designing and characterizing binders for extended peptides in which the loops form one side of an extended binding pocket. The ability to design multiple structured loops should contribute generally to efforts to design new protein functions.

Indexed as

Hydrogen BondingModels, MolecularProteinsAmino Acid SequenceBinding SitesCrystallography, X-RayPeptidesProtein ConformationProtein EngineeringProtein FoldingPeptidesProteins

Identifiers

PMID38816644
PMCPMC11288887

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.