High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials

Maria J. Solares, G. M. Jonaid, William Y. Luqiu, Samantha Berry, Janki Khadela, Yanping Liang, Madison C. Evans, Kevin J. Pridham, William J. Dearnaley, Zhi Sheng, Deborah F. Kelly

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Mutations in tumor suppressor genes, such as Tumor Protein 53 (TP53), are heavily implicated in aggressive cancers giving rise to gain- and loss-of-function phenotypes. While individual domains of the p53 protein have been studied extensively, structural information for full-length p53 remains incomplete. Functionalized microprocessor chips (microchips) with properties amenable to electron microscopy permitted us to visualize complete p53 assemblies for the first time. The new structures revealed p53 in an inactive dimeric state independent of DNA binding. Residues located at the protein-protein interface corresponded with modification sites in cancer-related hot spots. Changes in these regions may amplify the toxic effects of clinical mutations. Taken together, these results contribute advances in technology and imaging approaches to decode native protein models in different states of activation.

Original languageEnglish (US)
Article numbere202200310
JournalChemBioChem
Volume23
Issue number17
DOIs
StatePublished - Sep 5 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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