Eduardo Perozo
Research Summary / Selected Publications
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?
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?...
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
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.
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
Chakrapani, S., Cordero-Morales, JF., Perozo, E. (2007) A Quantitative description of KcsA gating II: Single Channel Currents. Journal of General Physiology 130: 479-496.
Chakrapani, S., Cordero-Morales, JF., Perozo, E. (2007) A Quantitative description of KcsA gating I: Macroscopic Currents. Journal of General Physiology 130: 465-478.
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
Cordero-Morales, J. F., Cuello, L. G., Zhao, Y., Jogini, V., Cortes, D. M., Roux, B. and Perozo, E. (2006). "Molecular determinants of gating at the potassium-channel selectivity filter." Nat Struct Mol Biol 13: 311-8.
Cordero-Morales, J. F., Cuello, L. G. and Perozo, E. (2006). "Voltage-dependent gating at the KcsA selectivity filter." Nat Struct Mol Biol 13: 319-22.
Cuello, L. G., Cortes, D. M. and Perozo, E. (2004). "Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer." Science 306: 491-5.
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
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.
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
Chakrapani, S., Cordero-Morales, JF., Perozo, E. (2007) A Quantitative description of KcsA gating II: Single Channel Currents. Journal of General Physiology 130: 479-496.
Chakrapani, S., Cordero-Morales, JF., Perozo, E. (2007) A Quantitative description of KcsA gating I: Macroscopic Currents. Journal of General Physiology 130: 465-478.
