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Professor, Biochemistry & Molecular Biokogy, Institute for Biophysical Dynamics; Pritzker Fellow, The University of Chicago
Affiliation: Biochemistry & Molecular Biology, Institute for Biophysical Dynamics
Ion channels, membrane transport, membrane protein dynamics, energy transduction mechanisms, voltage dependent processes. Over-expression of membrane proteins
Universidad Central de Venezuela, Caracas, Facultad de Ciencias, Licenciado , 1980‑1985, Biology
University of California, Los Angeles, Ph.D., 1987-1990, Physiology
University of California, Los Angeles, Post Doc, 1991-1993, Membrane Biophysics
May‑Aug 1986 Grass Fellow. Grass Foundation, Marine Biological Laboratory. Woods Hole, Massachusetts.
1987 Chancellor's Fellow. University of California, Los Angeles
1989 Kugel Foundation Fellow, Department of Physiology, University of California, Los Angeles
1990 John Field Award, Department of Physiology, University of California, Los Angeles, CA.
1991- 1993 PEW Charitable Trust Latin American Fellowship, University of California, Los Angeles, CA.
1994 PPI Program Fellow, Level II. Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICIT) Caracas, Venezuela.
1998-2000 McKnight Fellow, University of Virginia.
2000 SOBLA Prize, Latin-American Society of Biophysicists. Alicante, Spain.
2004 Kuffler/MBL Fellowships. Marine Biological Laboratory, Woods Hole, MA.
2006-present Pritzker Fellow, The University of Chicago
Most membrane proteins have moving parts that help execute their specific function, often in response to an external stimulus. Our research aims to understand the molecular mechanisms underlying the transduction of different forms of energy into protein motion; in particular the different molecular mechanisms of ion channel gating. We are equally interested in protein structure as in protein dynamics, for it is the dynamic behavior of a molecule what links structure to function.
Therefore, we rely on spectroscopic methods, and in particular reporter group techniques (EPR, Fluorescence), to study channels and other membrane proteins embedded in a fluid lipid bilayer. Static structural analyses are pursued by X-ray crystallography. These structural techniques are all interpreted in the context of high-resolution functional methods (single channel, macroscopic and gating current electro-physiological measurements). Using these strategies, we aim to answer the following long-term questions:
1- What is the structural pathway followed in the transition from the closed to the open conformation in K+ channels, and what is the nature of this conformational wave?
2- What is the influence of the selectivity filter on channel gating?
3- What is the native structure of voltage-dependent channels and how is transmembrane voltage sensed?
4- How do voltage sensor and gate couple to open the channel?
5- What is the molecular basis of mechanosensitivity in prokaryotic channels? How do membrane bilayer deformations are transduced into large protein rearrangements leading to channel opening?
- Cordero-Morales, JF., Jogini, V., Lewis, A., Vásquez, V., Cortes, D.M., Roux, B., and Perozo, E. (2007) Molecular Driving Forces Determining Potassium Channel Slow Inactivation. Nature Structural & Molecular Biology, 14:1062-1069 No PCMID
- Cuello, LG, Jogini, V., Cortes, DM, Perozo, E. (2010) Structural mechanism of C-type inactivation in K(+) channels.. Nature 466:203-208 PMCID: PMC3033749
- Cuello, LG, Cordero-Morales, J., Jogini, V., Perozo, E. (2010) Structural basis for the coupling between activation and inactivation gates in K(+) channels.. Nature 466:272-275 PMCID: PMC3033755
- Cuello LG, Cortes DM, Perozo E. (2004). Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer. Science. 306(5695):491-5. No pcmid
- Chakrapani, S., Cuello, LG., Perozo, E. (2008) Structural Dynamics of the Isolated-Voltage Sensor Domain of KvAP in Lipid Bilayer. Structure 16(3):398-409 PMCID: PMC2703488
- Vásquez, V., Sotomayor, M., Cordero-Morales, J., Schulten, K., and Perozo E. (2008) A Structural Mechanism for MscS Gating in Lipid Bilayers. Science, 321:1210-4. PMCID: PMC2897165
- Uysal, S., Vásquez, V., Terechko, V., Esaki, K., Koide, S., Fellouse, FA, Sidhu, SS, Perozo, E. and Kossiakoff, A. (2009) The Crystal Structure of Full-Length KcsA in its Closed Conformation. PNAS 106:6644-9 PMCID: PMC2672561
- Dalmas, O., Cuello, LG, Jogini, V., Cortes, DM., Roux, B., Perozo E., (2010) Structural Dynamics of the Magnesium-bound Conformation of CorA in a lipid bilayer. Structure 18: 868-878 PMCID: PMC2935691
- Chakrapani, S., Cordero-Morales, JF., Jogini, V., Pan, AC, Cortes, DM, Roux, B., Perozo, E. (2011) On the structural basis of modal gating behavior in K+ channels. Nature Structural & Molecular Biology 18:67-74 PMCID: PMC3059741
- Cordero-Morales, JF., Jogini, V., Chakrapani, S., Perozo, E. (2011) A Multipoint Hydrogen Bond Network Underlying KcsA C-type Inactivation. Biophysical Journal, 100(10):2387-2393. PMCID: PMC3093550
- Uysal, S., Cuello, LG., Cortes, DM., Koide, S., Kossiakoff, A., and Perozo, E. (2011) Mechanism of Activation Gating in the Full-Length KcsA K+ Channel. Proc. Natl. Acad. Sci. USA, 108(29):11896-11899. PMCID: PMC3141920
- Ferrer-Villada T, Cordero-Morales JF, Arias M, Ficker E, Medovoy D, Perozo E, Tristani-Firouzi M (2011) Molecular coupling in the human ether-a-go-go-related (hERG) K+ channel inactivation pathway. J Biol Chem 286(45):39091-9 PMCID: PMC3234734
- Pan AC, Cuello LG, Perozo E, Roux B. (2011) Thermodynamic coupling between activation and inactivation gating in potassium channels revealed by free energy molecular dynamics simulations. J Gen Physiol.138(6):571-80. PMCID: PMC3226968
- L. G. Cuello, V. Jogini, D. M. Cortes, A. C. Pan, D. G. Gagnon, O. Dalmas, J. F. Cordero-Morales, S. Chakrapani, B. Roux & E. Perozo. Structural basis for the coupling between activation and inactivation gates in K(+) channels. Nature 466, 272-275, (2010) PMCID: PMC3033755.
- E. Vargas, V. Yarov-Yarovoy, F. Khalili-Araghi, W.A. Catterall, M.L. Klein, M.E, Tarek, K. Lindahl, K. Schulten, E. Perozo, F. Bezanilla, B. Roux. An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations. J Gen Physiol. 140(6):587-94. (2012) PMCID: PMC3514734.
- Torbeev VY, Raghuraman H, Hamelberg D, Tonelli M, Westler WM, Perozo E, Kent SB. Protein conformational dynamics in the mechanism of HIV-1 protease catalysis..Proc Natl Acad Sci U S A. 108(52):20982-7. PMCID: PMC3248522