ChemBioChem · 2022 · 12 citations · 33 references
Life SciencesMolecular BiologyOncologyMolecular Cell BiologyMolecular OncologyStructural BiologyMacromolecular AssemblyMacromolecular Structure DeterminationMolecular Imaging In OncologyProtein StructureTumor ImagingCancer-on-chip ModelsMacromolecular Structure VisualizationP53 InactivationP53 MutationPost-translational Modification SitesTp53 MutationsTumor Suppressor LossTumor Suppressor P53
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.
33
The Phyre2 web portal for protein modeling, prediction and analysis
Lawrence A. Kelley, Stefans Mezulis, Christopher M. Yates et al. · Nature Protocols · 2015 · 10.2K citations · Full text
Dorothée Liebschner, Pavel V. Afonine, Matthew L. Baker et al. · Acta Crystallographica Section D Structural Biology · 2019 · 7.4K citations · Full text
The Somatic Genomic Landscape of Glioblastoma
Cameron Brennan, Roel G.W. Verhaak, Aaron McKenna et al. · Cell · 2013 · 5.2K citations · Full text