Education

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

Biography

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

BPHYS Students

David Medovoy, PhD

Young Hoon Koh

Research Summary

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?

Selected Papers

Zhao R, Dai H, Arias RJ, De Blas GA, Orta G, Pavarotti MA, Shen R, Perozo E, Mayorga LS, Darszon A, Goldstein SAN. Direct activation of the proton channel by albumin leads to human sperm capacitation and sustained release of inflammatory mediators by neutrophils. Nat Commun. 2021 06 22; 12(1):3855. View in: PubMed

Li J, Shen R, Reddy B, Perozo E, Roux B. Mechanism of C-type inactivation in the hERG potassium channel. Sci Adv. 2021 Jan; 7(5). View in: PubMed

Clark MD, Contreras GF, Shen R, Perozo E. Electromechanical coupling in the hyperpolarization-activated K+ channel KAT1. Nature. 2020 07; 583(7814):145-149. View in: PubMed

Reddy B, Bavi N, Lu A, Park Y, Perozo E. Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS. Elife. 2019 12 27; 8. View in: PubMed

Rangl M, Schmandt N, Perozo E, Scheuring S. Real time dynamics of Gating-Related conformational changes in CorA. Elife. 2019 11 27; 8. View in: PubMed

Li J, Zhang J, Tang W, Mizu RK, Kusumoto H, XiangWei W, Xu Y, Chen W, Amin JB, Hu C, Kannan V, Keller SR, Wilcox WR, Lemke JR, Myers SJ, Swanger SA, Wollmuth LP, Petrovski S, Traynelis SF, Yuan H. De novo GRIN variants in NMDA receptor M2 channel pore-forming loop are associated with neurological diseases. Hum Mutat. 2019 12; 40(12):2393-2413. View in: PubMed

Zhao R, Kennedy K, De Blas GA, Orta G, Pavarotti MA, Arias RJ, de la Vega-Beltrán JL, Li Q, Dai H, Perozo E, Mayorga LS, Darszon A, Goldstein SAN. Role of human Hv1 channels in sperm capacitation and white blood cell respiratory burst established by a designed peptide inhibitor. Proc Natl Acad Sci U S A. 2018 12 11; 115(50):E11847-E11856. View in: PubMed

Li J, Ostmeyer J, Cuello LG, Perozo E, Roux B. Rapid constriction of the selectivity filter underlies C-type inactivation in the KcsA potassium channel. J Gen Physiol. 2018 10 01; 150(10):1408-1420. View in: PubMed

Lau C, Hunter MJ, Stewart A, Perozo E, Vandenberg JI. Never at rest: insights into the conformational dynamics of ion channels from cryo-electron microscopy. J Physiol. 2018 04 01; 596(7):1107-1119. View in: PubMed