Mesoscopic protein-rich clusters host the nucleation of mutant p53 amyloid fibrils
Abstract
The mesoscopic p53-rich clusters that we discover represent a new class of biological condensate, distinct from amorphous and ordered aggregates and the dense liquids found with several physiologically active proteins. The demonstrated two-step mechanism of amyloid fibril nucleation, whereby the clusters host the nucleation of p53 amyloid fibrils, illustrates the potency of recently identified nonclassical nucleation concepts to understand intracellular processes. This finding establishes a new biophysical paradigm for the assembly of numerous ordered functional and pathological biological solids, such as tubules, filaments, sickle cell polymers, amyloids, and crystals.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 02, 2021
- Source ID
- 10.1073/pnas.2015618118
Entities
People
- Alena Klindziuk
- Anatoly B Kolomeisky
- Aram Davtyan
- Arash Saeedi
- David S. Yang
- Michael B. Sherman
- Michelle C. Barton
- Mohammad S. Safari
- Mohsen Fathi
- Navin Varadarajan
- Peter G Vekilov
Organizations
- Cancer Prevention and Research Institute of Texas
- Congressionally Directed Medical Research Programs
- Division of Materials Research
- Division of Physics
- Marshall Space Flight Center
- Melanoma Research Alliance
- National Institute of Allergy and Infectious Diseases
- Princeton University
- Rice University
- University of Houston
- University of Texas Medical Branch
- University of Texas at Austin