Dr. Rui Sousa's lab uses 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
Currently they 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
In addition, they 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.
Morgan JR, Jiang J, Oliphint PA, Jin S, Gimenez LE, Busch DJ, Foldes AE, Zhuo Y, Sousa R, Lafer EM. A role for an Hsp70 nucleotide exchange factor in the regulation of synaptic vesicle endocytosis. J Neurosci. 2013 May 1;33(18):8009-21.
Sousa R, Jiang J, Lafer EM, Hinck AP, Wang L, Taylor AB, Maes EG. Evaluation of competing J domain:Hsp70 complex models in light of existing mutational and NMR data. Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):E734; author reply E735.
Velazquez G, Guo Q, Wang L, Brieba LG, Sousa R. Conservation of promoter melting mechanisms in divergent regions of the single-subunit RNA polymerases. Biochemistry. 2012 May 8;51(18):3901-10.
Li Y, Sousa R. Expression and purification of E. coli BirA biotin ligase for in vitro biotinylation. Protein Expr Purif. 2012 Mar;82(1):162-7.
Li Y, Sousa R. Novel system for in vivo biotinylation and its application to crab antimicrobial protein scygonadin. Biotechnol Lett. 2012 Sep;34(9):1629-35.