puc-header

Dense Liquid Condensates Host the Nucleation of Tumor Suppressor p53 Fibrils

36 Pages Posted: 29 Jan 2019 Sneak Peek Status: Published

See all articles by Mohammad S. Safari

Mohammad S. Safari

University of Houston - Department of Chemical and Biomolecular Engineering

Zhiqing Wang

University of Houston - Department of Chemical and Biomolecular Engineering

Kunaal Tailor

University of Houston - Department of Chemical and Biomolecular Engineering

Anatoly B. Kolomeisky

Rice University - Department of Chemistry

Jacinta C. Conrad

University of Houston - Department of Chemical and Biomolecular Engineering

Peter G. Vekilov

University of Houston - Department of Chemical and Biomolecular Engineering

More...

Abstract

About half of human cancers are associated with mutations of the tumor suppressor p53. Gained oncogenic functions of the mutants have been related to aggregation behaviors of wild-type and mutant p53. The thermodynamic and kinetic mechanisms of p53 aggregation are poorly understood. Here we find that wild-type p53 forms an anomalous liquid phase. The liquid condensates exhibit several behaviors beyond the scope of classical phase transition theories: their size, ca. 100 nm, is independent of the p53 concentration and decoupled from the protein mass held in the liquid phase. Thermodynamic analyses elucidate another unusual property of this liquid phase: lack of constant solubility. The nucleation of p53 fibrils deviates from the accepted mechanism of sequential association of single solute molecules. We find the liquid condensates serve as pre-assembled precursors of high p53 concentration that facilitate fibril assembly. Fibril nucleation hosted by precursors represents a novel biological pathway, which opens avenues to suppress protein fibrillation in aggregation diseases.

Suggested Citation

Safari, Mohammad S. and Wang, Zhiqing and Tailor, Kunaal and Kolomeisky, Anatoly B. and Conrad, Jacinta C. and Vekilov, Peter G., Dense Liquid Condensates Host the Nucleation of Tumor Suppressor p53 Fibrils (September 14, 2018). Available at SSRN: https://ssrn.com/abstract=3249470 or http://dx.doi.org/10.2139/ssrn.3249470
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Mohammad S. Safari

University of Houston - Department of Chemical and Biomolecular Engineering

Houston, TX 77204
United States

Zhiqing Wang

University of Houston - Department of Chemical and Biomolecular Engineering

Houston, TX 77204
United States

Kunaal Tailor

University of Houston - Department of Chemical and Biomolecular Engineering

Houston, TX 77204
United States

Anatoly B. Kolomeisky

Rice University - Department of Chemistry

6100 South Main Street
Houston, TX 77005-1892
United States

Jacinta C. Conrad

University of Houston - Department of Chemical and Biomolecular Engineering

Houston, TX 77204
United States

Peter G. Vekilov (Contact Author)

University of Houston - Department of Chemical and Biomolecular Engineering ( email )

Houston, TX 77204
United States

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
230
Downloads
10