Department of Pediatrics
Institute of Molecular Pediatric Sciences
Committee on Molecular Medicine/MPMM
Phone: (773) 834-4747
The University of Chicago
929 East 57th Street
Chicago, IL 60637
Related Research Interests:
Eduardo Perozo, Ph.D.
Structure-Function and Energy Transduction Mechanisms
in Ion Channels Using Functional Spectroscopic and Structural Approaches
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
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?
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. PMID: 15486302
[PubMed - indexed for MEDLINE]
Ptak CP, Cuello LG, Perozo E. (2005). Electrostatic interaction of a K+
channel RCK domain with charged membrane surfaces. Biochemistry. 44(1):62-71. PMID: 15628846
[PubMed - indexed for MEDLINE]
Sale K, Song L, Liu YS, Perozo E, Fajer P. (2005). Explicit
treatment of spin labels in modeling of distance constraints from
dipolar EPR and DEER. J Am Chem Soc.
127(26):9334-5. No abstract available. PMID: 15984837 [PubMed - indexed
Perozo E. Gating prokaryotic mechanosensitive channels. Nat Rev Mol Cell Biol.
2006 Feb;7(2):109-19. Review. PMID: 16493417 [PubMed - indexed for
Cordero-Morales JF, Cuello LG, Perozo E. Voltage-dependent gating at
the KcsA selectivity filter. (2006). Nat Struct Mol Biol.
13(4):319-22. Epub 2006 Mar 12. PMID: 16532008 [PubMed - indexed for
Cordero-Morales JF, Cuello LG, Zhao Y, Jogini V, Cortes DM, Roux B,
Perozo E. (2006). Molecular determinants of gating at the
potassium-channel selectivity filter. Nat Struct Mol Biol.
13(4):311-8. Epub 2006 Mar 12. PMID: 16532009 [PubMed - indexed for
Blunck R, Cordero-Morales JF, Cuello LG, Perozo E, Bezanilla F. (2006).
Detection of the opening of the bundle crossing in KcsA
with fluorescence lifetime spectroscopy reveals the existence of two
gates for ion conduction. J Gen Physiol.
128(5):569-81. Epub 2006 Oct 16. PMID: 17043150 [PubMed - in process]
Sotomayor M, Vasquez V, Perozo E, Schulten K. Ion Conduction through
MscS as Determined by Electrophysiology and Simulation. Biophys J. 2006 Nov 17; [Epub ahead
of print] PMID: 17114233 [PubMed - as supplied by publisher]
Faculty and Research