Rui J. Sousa, PhD



We use a combination of X-ray crystallography, mutational analyses, and a variety of biochemical and biophysical approaches to understand how conformationally dynamic macromolecular machines carry out their cellular reactions. Currently we are studying two systems: the single subunit RNA polymerases (especially the mitochondrial RNA polymerase), and the Hsp70 chaperons and their co-chaperons. Both of these systems are characterized by proteins that induce large conformational changes in the substrates that they act upon, and do so by themselves undergoing large conformation changes. The biological activities of these particular molecules the mitochondrial RNA polymerase and the Hsp70 chaperons are essential to cell function and their roles in aging and diseases such as cancer and neurodegeneration are becoming increasingly recognized, making them active targets of biomedical investigation and drug development.

In addition we are also beginning a new project to engineer proteins that can act as in vivo probes of the concentrations of GTP and GDP, molecules that play critical roles in regulating cell metabolism.

Biology and Mechanism of the Single Subunit RNA Polymerases;

Structure and Mechanism of the Hsp70 Chaperones and Co-Chaperones;

Roles of the Hsp70 chaperones and cochaperones in vesicle trafficking;