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.
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.
What it found
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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.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Protein Engineering-Enabled Cryo-EM Investigation of Small GTPases.Journal of molecular biology · 2026Article
- High-resolution cryo-EM structures of small protein-ligand complexes near the theoretical size limit.Nature communications · 2026Article
- Review
- Trimbody with rigid AI-designed scaffolds enables atomic-resolution cryo-EM structure determination of small proteins.Nature communications · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Strategic advances for cryo-EM structural studies of small (<100 kDa) GPCRs.Communications biology · 2026Review
- Covalently constrained 'Di-Gembodies' enable parallel structure solutions by cryo-EM.Nature chemical biology · 2026Article
- Antibody-enabled structural biology and AI-driven antibody design.Frontiers in pharmacology · 2026Review
- Hidden gems bring proteins into view.Nature chemical biology · 2026Article
- Structural determination of small proteins by cryo-EM using a coiled coil module strategy.Scientific reports · 2025Article
- Computational design of bifaceted protein nanomaterials.Nature materials · 2025Article
- Structures of a synthetic antibody selected against and bound to the C-terminal domain of Clostridium perfringens enterotoxin.Protein science : a publication of the Protein Society · 2025Article
- Disulfide-constrained Fabs overcome target size limitation for high-resolution single particle cryoEM.Nature communications · 2025Article
- Local structural flexibility drives oligomorphism in computationally designed protein assemblies.Nature structural & molecular biology · 2025Article
- Nonviral protein cages as tools to decipher and combat viral threats.Npj viruses · 2025Review
- Article
- Nanopore sensing of protein and peptide conformation for point-of-care applications.Nature communications · 2025Review
- A fiducial-assisted strategy compatible with resolving small MFS transporter structures in multiple conformations using cryo-EM.Nature communications · 2025Article
- CryoEM grid preparation: a closer look at advancements and impact of preparation mode and new approaches.Biochemical Society transactions · 2024Review
- A suite of designed protein cages using machine learning and protein fragment-based protocols.Structure (London, England : 1993) · 2024Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
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.
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Registered trials
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.