Principles of Protein Assembly, From Molecules to Cells
Emmanuel Levy (Weizmann Institute of Science, Israel)
Life processes involve an intricate choreography between tens of millions of protein building blocks that form the infrastructure of cells. Recent technological advances have revealed the catalogs of proteins present in various cells and organisms. However, understanding how these protein building-blocks assemble and work together is an extraordinarily complex task. I will present our work aimed at addressing this challenge. First, I will describe how stickiness, defined as the chemical propensity of protein surfaces to bind to each other, is tuned across entire proteomes to minimize promiscuous interactions. Second, I will show that even single point-mutations changing the surface stickiness of homo-oligomeric proteins can trigger their infinite folded-state self-assembly. Finally, I will describe the design of synthetic protein condensates with tractable and tunable phase behavior; and work-in-progress, on how we are using these condensates to identify genes globally regulating macromolecular self-assembly in cells.