Structural investigation of cholesterol homeostasis and bacterial toxins

Abstract

Membrane proteins regulate a variety of processes that are critical for living organisms. They participate in cell-cell communication, catalyze reactions in or at the membrane, are involved in transmitting signals from the environment into the cell, and can transport molecules across membranes. Approximately 60% of all clinically approved drugs target membrane proteins, underscoring their importance. In order to understand the function of membrane proteins and to design more targeted drugs, determining their precise three-dimensional structures is required. In this PhD project, I aimed to structurally characterize two membrane protein complexes involved in the regulation of cholesterol homeostasis – the Scap-Insig and HMGCR-UBIAD1 complexes – and the type VI secretion system (T6SS) effector RhsA. My PhD work showcases that biochemical studies combined with structural determination by cryo-EM provides valuable insights into molecular processes that occur in or at the membrane and is of utmost pharmacological interest.