|
We run on electricity. Brains, muscles, hearts, and
senses all require electrical signals to function properly. Our research
aims to understand the basic components of excitable cells that are
responsible for generating electrical activity. To this end, we focus
on understanding the structure, function, and regulation of ion channels
from a high-resolution viewpoint. Our lab is multidisciplinary and
combines approaches that include X-ray crystallographic studies, biochemistry,
molecular biology, selection from combinatorial libraries, and electrophysiology
to understand the basic mechanisms of how these proteins function
and are regulated.
Ion channels are membrane proteins that allow cells to generate electrical
signals. They are found not only in excitable cells like neurons and
muscle, but are ubiquitous in biological systems. These proteins act
as gates, specifically controlling the flux of ions across the cell's
membrane in the response to a variety of stimuli including transmembrane
voltage changes, ligand binding, and second messenger stimulation.
Generally, channel proteins exist in one of two conformations, open
or closed. In the open state, ion channels form a pathway that allows
ions flow down their electrochemical gradients from one side of the
cell membrane to the other. Control of ion flux in response to external
stimulation, generates the fundamental signaling step that forms the
basis for many biological processes such as the regulation of heartbeat,
movement of muscle, regulation of hormone release from pancreatic
cells, and the generation of thought. Many types of ion channels are
known. Channels that specifically conduct potassium ions constitute
the largest, most diverse family of ion channels and play key roles
in the regulation of cell excitability. We are interested in understanding
the mechanisms by which these proteins act. What are principal rules
that govern ion channel structure? What is the nature of the conformational
changes that accompany channel activation? How does a cell modulate
channel activity through the action of proteins like kinases and GTPases?
Can we develop new methods to modulate ion channel function in vivo?
Addressing the molecular basis of these issues will be critical to
understanding the roles of ion channels in larger signaling networks,
like the brain, as well as understanding their misfunction in various
human diseases. |
Van Petegem, F., Clark, K.A., Chatelain, F.C., and Minor, D.L., Jr. , "Structure of a complex between a voltage gated calcium channel β-subunit and an α-subunit domain" Nature 429 671-675 (2004)
Minor, D.L., Jr. Potassium Channels: life in
the post-structural world. Current Opinion in Structural Biology
11 408-414 (2001)
Minor, D.L., Jr., Lin, Y.F, Mobley, B.C., Avelar, A., Jan, Y.N.,
Jan, L.Y. and Berger, J.M. The polar T1 interface is linked to conformational
changes that open the voltage-gated potassium channel. Cell 102
657-670 (2000).
Minor, D.L., Jr., Masseling, S.J., Jan, Y.N. and Jan, L.Y. Transmembrane
structure of an inwardly rectifying potassium channel. Cell 96 879-891
(1999).
Minor, D.L., Jr. and Kim P.S. Context-dependent secondary structure
formation of a designed protein sequence. Nature 380 730-734 (1996).
Schumacher, T.N.M., Mayr, L.M., Minor, D.L., Jr., Milhollen, M.A.,
Burgess, M.W. and Kim, P.S. Identification of (D)-peptide ligands
through Mirror-Image phage display. Science 271 1854-1857 (1996).
Minor, D.L., Jr. and Kim P.S. Context is a major determinant of
b-sheet propensity. Nature 371 264-267 (1994).
Minor, D. L., Jr. and Kim P. S. Measurement of the b-sheet forming
propensities of amino acids. Nature 367 660-663 (1994).
information last updated June 2005 |
Biomedical Sciences (BMS) Graduate Program
