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Molecular
Basis of Electrical Signaling 
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.
Selected Publications:
Minor, D. L., Jr. and Kim P. S. Measurement of the b-sheet forming propensities
of amino acids. Nature 367 660-663 (1994).
Minor, D.L., Jr. and Kim P.S. Context is a major determinant of b-sheet
propensity. Nature 371 264-267 (1994).
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-dependent secondary structure formation
of a designed protein sequence. Nature 380 730-734 (1996).
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., 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. Potassium Channels: life in the post-structural world.
Current Opinion in Structural Biology 11 408-414 (2001)
Contact Information:
Email: minor@itsa.ucsf.edu
Phone: 415/ 514-2552
Address: Box 0130, Room HSE 1308
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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