Evidence map›Paper›PMID 37669364›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Cryo-EM structure determination of small therapeutic protein targets at 3 Å-resolution using a rigid imaging scaffold.

Roger Castells-Graells, Kyle Meador, Mark A Arbing, Michael R Sawaya, Morgan Gee, Duilio Cascio, Emma Gleave, Judit É Debreczeni, Jason Breed, Karoline Leopold and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
12.2field-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

30 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Hidden gems bring proteins into view.Nature chemical biology · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
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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

16 authors at 3 institutions in 3 countries.

Roger Castells-GraellsDepartment of Energy, Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095.ORCID 0000-0002-3985-6194
Kyle MeadorDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.ORCID 0000-0001-5049-027X
Mark A ArbingDepartment of Energy, Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095.ORCID 0000-0002-6684-1430
Michael R SawayaDepartment of Energy, Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095.ORCID 0000-0003-0874-9043
Morgan GeeDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.ORCID 0009-0000-2015-649X
Duilio CascioDepartment of Energy, Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095.ORCID 0000-0001-8285-754X
Emma GleaveDiscovery Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom.
Judit É DebreczeniDiscovery Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom.
Jason BreedDiscovery Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom.
Karoline LeopoldGandeeva Therapeutics, Inc., Burnaby, British Columbia V5C 6N5, Canada.ORCID 0000-0001-5904-5076
Ankoor PatelGandeeva Therapeutics, Inc., Burnaby, British Columbia V5C 6N5, Canada.ORCID 0000-0002-9096-1619
Dushyant JahagirdarGandeeva Therapeutics, Inc., Burnaby, British Columbia V5C 6N5, Canada.ORCID 0000-0003-4173-7378
Bronwyn LyonsGandeeva Therapeutics, Inc., Burnaby, British Columbia V5C 6N5, Canada.
Sriram SubramaniamGandeeva Therapeutics, Inc., Burnaby, British Columbia V5C 6N5, Canada.ORCID 0000-0003-4231-4115
Chris PhillipsDiscovery Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom.ORCID 0000-0001-6569-9025
Todd O YeatesDepartment of Energy, Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095.ORCID 0000-0001-5709-9839
University of California, Los Angeles · USAstraZeneca (United Kingdom) · GBUniversity of British Columbia · CA

Funding

Designing Novel Protein Assemblies as Rigid Symmetric Scaffolds for Cryo-EM ImagingR01GM129854 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YEATES, TODD O · 2019 to 2022
$1.2M
NIGMS NIH HHS R01 GM129854
6 · The paper itself

Abstract

Cryoelectron microscopy (Cryo-EM) has enabled structural determination of proteins larger than about 50 kDa, including many intractable by any other method, but it has largely failed for smaller proteins. Here, we obtain structures of small proteins by binding them to a rigid molecular scaffold based on a designed protein cage, revealing atomic details at resolutions reaching 2.9 Å. We apply this system to the key cancer signaling protein KRAS (19 kDa in size), obtaining four structures of oncogenic mutational variants by cryo-EM. Importantly, a structure for the key G12C mutant bound to an inhibitor drug (AMG510) reveals significant conformational differences compared to prior data in the crystalline state. The findings highlight the promise of cryo-EM scaffolds for advancing the design of drug molecules against small therapeutic protein targets in cancer and other human diseases.

Indexed as

Diagnostic ImagingCryoelectron MicroscopyHumanscancer drugscryo-EMimaging scaffoldsprotein designsmall proteins

Identifiers

PMID37669364
PMCPMC10500258
OpenAlexW4386453144

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.