Office: Jennie Smoly Caruthers Biotech Building, Room A417
Lab: JSCBB A480 (4th floor, A wing)
Lab Phone: 303-735-6334
Ph.D.: University of Buenos Aires, 1995
Pharm. D. University of Buenos Aires, 1989
Postdoctoral Fellow: School of Medicine Stanford University, 1995-2001
Awards:New Scholar in Global Infectious Disease. The Ellison Medical Foundation (2004)Junior Faculty Development Award. University of Colorado at Boulder (2003)Scientist Development Award. American Heart Association (2003-present)
Molecular Biophysics, Proteins & Enzymology, Structural Biology
Our research program seeks to understand, in molecular detail, fundamental cellular processes that occur at the membrane interface. We utilize a multidisciplinary approach in our program. X-ray crystallography is our main tool to obtain high-resolution structures and macromolecular mechanisms are elucidated with complementary biochemical and biophysical studies including NMR, Small Angle X-Ray Scattering and EM.
Three fundamental membrane-related systems are the focus of our program:
(i) Folding and Insertion of Membrane Proteins in the Bacterial and Mitochondrial Outer Membrane: We seek to understand the molecular mechanisms by which chaperones and the BAM membrane protein complex cooperate to promote folding and specific insertion of b-barrel OMPs into bacterial and mitochondrial outer membranes.
(ii) Modification of the Bacterial Outer Membranes Mediating Antibiotic Resistance: Lipid-A modification with Ara4N confers resistance antimicrobial peptides of the innate immune system as well as antibiotics such as colistin. The focus of our research is to determine the structure and mechanism of enzymes essential for Lipid-A modification with Ara4N as a key for the design and evaluation of specific inhibitors.
(iii) Signaling Pathways at the Membrane Interface: Membrane-bound Guanylyl Cyclases: We seek to determine the molecular basis for disease causing mutations in GCs as well as validating the hypothesis of a conserved activation mechanism for all members of the membrane-GCs family.
Walton, T. A. & Sousa, M. C. “Crystal Structure of Skp. A Prefoldin-like Chaperone that Protects Soluble and Membrane Proteins from Aggregation”
Molecular Cell. (2004) 15(3):367-74.
Gatzeva-Topalova, PZ; May, A and Sousa M.C. “Crystal Structure of E. coli ArnA (PmrI) Decarboxylase Domain. A Key Enzyme for LipidA Modification with 4-amino-4deoxy-L-arabinose and Polymyxin Resistance.”
Biochemistry. (2004) 43 (42):13370-9. PMCID: PMC2680612
Gatzeva-Topalova, PZ; May, A and Sousa M.C. “Crystal Structure and Mechanism of E. coli ArnA (PmrI) Transformylase Domain. An Enzyme for Lipid A Modification with 4-amino-4-deoxy-L-arabinose and Polymyxin Resistance "
Biochemistry. (2005) 44 (14): 5328-5338. PMCID: PMC2583347
Gatzeva-Topalova, PZ; May, A and Sousa M.C. “Structure and Mechanism Of ArnA-A Key Enzyme For Polymyxin Resistance. Conformational Change Implies Ordered Dehydrogenase Mechanism."
Structure. (2005) 13 (6): 929-42 [Cover Feature].
Stephen, R.; Palczewski, K. and Sousa M.C. “The Crystal Structure of GCAP3 Suggests Molecular Mechanism of GCAP–linked Cone Dystrophies.”
J. Mol. Biol. (2006) 359 (2): 266-275.
Stephen, R.; Bereta, G.; Golczak, M.; Palczewski, K. and Sousa M.C. “Stabilizing Function for Myristoyl Group Revealed by the Crystal Structure of a Neuronal Calcium Sensor, Guanylate-Cyclase-Activating Protein 1”
Structure (2007) 15 (11): 1392-1402. PMCID: PMC2556213
Gatzeva-Topalova, P.Z.; Walton, T.A. and Sousa M.C. “Crystal Structure of YaeT - Conformational Flexibility and Substrate Recognition”.
Structure. (2008) 16 (12): 1873-1881. PMCDI: PMC2642521.
Walton, T.A.; Sandoval, C.M.; Fowler, C.A.; Pardi, A. and Sousa M.C. “The Cavity-Chaperone Skp Protects its Substrate from Aggregation but Allows Independent Folding of Substrate Domains”
PNAS (direct submission). (2009) 106 (10): 1772-1777. PMCID: PMC2644113
Gatzeva-Topalova, P.Z.; Warner, L.R.; Pardi, A. and Sousa M.C. “Structure and Flexibility of the Complete Periplasmic Domain of BamA. The Protein Insertion Machine of the Outer Membrane.”
Structure. (2010) 18(11):1492-501. PMCID: PMC2991101
Sandoval, C.M.; Baker S.L.; Jansen, K.; Metzner, S.I. and Sousa M.C. “Crystal Structure of BamD. An Essential Component of the b-Barrel Assembly Machinery of Gram Negative Bacteria.”
J. Mol. Biol. (2011) in press. PMCID: PMC3098899
Warner, L.R; Varga, K.; Lange, O.F.; Baker, S.L.; Baker, D.; Sousa, M.C. and Pardi A.
“Structure of the BamC two-domain protein obtained by Rosetta with a limited NMR data set.”
J. Mol. Biol. (2011) 411 (1): 83-95. PMCID: PMC3182476