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Neuroscience Graduate Program at UCSF

Faculty - Daniel L. Minor, Ph.D.

Structural and Mechanistic Studies of Ion Channels and Ion Channel Regulation


Research Description

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.

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Current Projects

Ion channel proteins control the passage of ions across the cell membrane and generate the bioelectricity that is essential for life.  Much of the future of neuroscience and cardiovascular research lies in understanding the molecular details of how these protein machines function, how they are regulated, and how they are integrated into large, macromolecular complexes within the cell.  To address these issues, our lab seeks to uncover the basic mechanisms by which ion channels act.  This ultimately requires a high-resolution structural description of the channel proteins, their regulatory factors, and the conformational changes that accompany channel action as well as the development of means to manipulate channel action in vivo

Research Topics

  1. Structural understanding of ion channel action and regulation
  2. Molecular evolution of ion channel modulators for channels
  3. Structural understanding of membrane proteins that power the cell through their actions in mitochondria

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Lab Members

Sviatoslav (Slav) Bagriantsev, Postdoctoral Fellow
Kim Clark, Research Specialist
Felix Findeisen, Postdoctoral Fellow
Christopher Kimberlin, Postdoctoral Fellow
Linlin Ma, Postdoctoral Fellow
Shalika Reddy Nurva, Research Technician
Dinesh Palanivelu, Postdoctoral Fellow
Christine Rumpf, Research Technician
David Shaya, Postdoctoral Fellow
Susan Shim, Research Technician
Stephanie Wong, Research Technician

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Selected Publications

Minor, D.L., Jr., "The neurobiologist's guide to structural biology: A Primer on why macromolecular structure matters and how to evaluate macromolecular structural data" Neuron 54 511-533 (2007)

Howard, R.J., Clark, K.A., Holton, J.M., and Minor, D.L., Jr., "Structural insight into KCNQ (Kv7) channel assembly and channelopathy" Neuron 53 663-675 (2007)

Pioletti, M., Findeisen, F., Hura, G.L., and Minor, D.L., Jr., "Three-dimensional structure of the KChIP/Kv4.3 T1 domain complex reveals a cross-shaped octamer" Nature Structural & Molecular Biology 13 987-995 (2006)

Van Petegem, F. and Minor, D.L., Jr., "The structural biology of voltage-gated calcium channel function and regulation" Biochemical Society Transactions 34 887-893 (2006)

Tsuruda, P., Julius, D., and Minor, D.L., Jr., "Coiled-coils direct assembly of a cold-activated TRP channel" Neuron 51 201-212 (2006)

Van Petegem, F, Chatelain, F.C., Minor, D.L., Jr., "Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex" Nature Structural & Molecular Biology 12 1108-1115 (2005)

Chatelain, F.C., Alagem, N., Xu, Q., Pancaroglu, R., Reuveny, E., and Minor, D.L., Jr., "The pore helix dipole has a minor role in inward rectifier channel function" Neuron 47 833-843 (2005)

Van Petegem, F., Clark, K., Chatelain, F., and Minor, D.L., Jr., "Structure of a complex between a voltage-gated calcium channel b-subunit and an a-subunit domain" Nature 429 671-675 (2004)

Minor, D.L., Jr., "Potassium channels: life in the post-structural world" Current Opinion in Structural Biology 11 403-407 (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)

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Daniel L. Minor, Ph.D.



Email

daniel.minor@ucsf.edu

Phone

415-514-2551

Physical Address

QB3
1700 4th Street
Room 303A

Mailing Address

UCSF
1700 4th Street
Box 2532
San Francisco, CA 94143-2532

For Internal Campus Mail

Box 2532

Other Websites

Biomedical Sciences Graduate Program

Lab Website

PIBS