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;
- Structure of the Hsp110:Hsc70 nucleotide exchange machine.
Schuermann JP, Jiang J, Cuellar J, Llorca O, Wang L, Gimenez LE, Jin S, Taylor AB, Demeler B, Morano KA, Hart PJ, Valpuesta JM, Lafer EM, Sousa R
Mol Cell: 2008-07-25; 31(2); 232-43 Epub: 2008-06-12.
PMID: 18550409 LINK:
- Mechanism of T7 RNAP pausing and termination at the T7 concatemer junction: a local change in transcription bubble structure drives a large change in transcription complex architecture.
Nayak D, Siller S, Guo Q, Sousa R
J Mol Biol: 2008-02-15; 376(2); 541-53 Epub: 2007-12-04.
PMID: 18166198 LINK:
- Structural basis of J cochaperone binding and regulation of Hsp70.
Jiang J, Maes EG, Taylor AB, Wang L, Hinck AP, Lafer EM, Sousa R
Mol Cell: 2007-11-09; 28(3); 422-33
PMID: 17996706 LINK:
- Structural basis of interdomain communication in the Hsc70 chaperone.
Jiang J, Prasad K, Lafer EM, Sousa R
Mol Cell: 2005-11-23; 20(4); 513-24
PMID: 16307916 LINK:
- Structural transitions mediating transcription initiation by T7 RNA polymerase.
Mukherjee S, Brieba LG, Sousa R
Cell: 2002-07-12; 110(1); 81-91
PMID: 12150999 LINK: