p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure-Function Continuum Concept.
Although it is one of the most studied proteins, p53 continues to be an enigma. This protein has numerous biological functions, possesses intrinsically disordered regions crucial for its functionality, can form both homo-tetramers and isoform-based hetero-tetramers, and is able to interact with many binding partners. It contains numerous posttranslational modifications, has several isoforms generated by alternative splicing, alternative promoter usage or alternative initiation of translation, and is commonly mutated in different cancers. Therefore, p53 serves as an important illustration of the protein structure-function continuum concept, where the generation of multiple proteoforms by various mechanisms defines the ability of this protein to have a multitude of structurally and functionally different states. Considering p53 in the light of a proteoform-based structure-function continuum represents a non-canonical and conceptually new contemplation of structure, regulation, and functionality of this important protein.
Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33612, USA. vuversky@health.usf.edu.|Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia. vuversky@health.usf.edu.
Vladimir N
VN
Uversky
D017398:Alternative Splicing; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D064267:Intrinsically Disordered Proteins; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53
alternative splicing; cancer; intrinsically disordered protein; mutation; p53; posttranslational modification; protein structure–function continuum; protein–protein interaction; proteoform