The Fall 2022 GWC2 Seminar Series continues with our next presentation Wednesday, October 12th. These seminars will be held in person in the Main Link room at the home University of the presenter, and via Teams for the opposite campus.
Elucidating Molecular Mechanisms in Protein Folding, Function and Aggregation
Professor Liz Meiering
Department of Chemistry
University of Waterloo
Wednesday, October 12, 2022
3:00 p.m.
C2-361 at the University of Waterloo - Coffee and snacks served.
Online via Microsoft Teams for the University of Guelph.
Please contact gwc@uoguelph.ca with your Teams ID/email address to attend the seminars online.
All are welcome to attend!
ABSTRACT: A major unsolved challenge in biochemistry is how protein folding and misfolding determine protein structure, function, and aggregation. These properties of proteins govern their behaviour in natural processes, disease, and biotechnology. We apply a battery of experimental and computational methods to elucidate the molecular mechanisms that govern the properties of proteins of fundamental and practical importance. In this seminar, I will present our research on three proteins: 1) Cu,Zn, superoxide dismutase, a ubiquitous enzyme in which mutations cause the devastating and invariably fatal neurodegenerative disease, amyotrophic lateral sclerosis; 2) adnectins (also known as monobodies), engineered proteins under development for binding diverse medical targets with high affinity and specificity; and 3) hisactophilin, a model for defining the allosteric mechanisms that control protein functional conformational switching. Using multidimensional heteronuclear NMR, mass spectrometry, and biochemical experiments in concert with computational methods, we have gained high-resolution views of 1) how SOD1 folds and aggregates, in solution and in cells, 2) the determinants of adnectin solubility, and 3) a fine balance of electrostatic and hydrophobic interactions that control pH-dependent switching function in hisactophilin. These findings illustrate how chemical and physical principles contribute to predicting and engineering the properties of these versatile and powerful biomolecules.