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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

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.

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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. Membrane proteins expression and structure

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Lab Members

Aram Chang, Postdoctoral Fellow
Kim Clark, Research Specialist/Lab Manager 
Felix Findeisen, Postdoctoral Fellow 
Christopher Kimberlin, Postdoctoral Fellow 
Hubing Lou, Postdoctoral Fellow
Gabriel Mercado, Postdoctoral Fellow 
Tina Nguyen, Postdoctoral Fellow
Shalika Reddy Nurva, Research Technician 
Ahmed Rohaim, Postdoctoral Fellow 
Christine Rumpf, Research Technician 
David Shaya, Postdoctoral Fellow 
Stephanie Wong
, Research Technician

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Selected Publications

Bagriantsev, S., Clark, K.A., and Minor, D.L., Jr., ‘Metabolic and thermal stimuli control K2P2.1 (TREK-1) through modular sensory and gating domains’ The EMBO Journal 31 3297-3308 (2012)

Liu L., Kohout, S.C., Xu, Q., Müller, S., Kimberlin, C.R., Isacoff, E.Y. Minor, D.L., Jr., ‘A glutamate switch controls voltage-sensitive phosphatase functionNature Structural and Molecular Biology 19 633-641 (2012)

Laggner, C., Kokel, D., Setola, V., Tolia, A., Lin, H., Irwin, J.J., Keiser, M.J., Minor, D.L., Jr., Roth, B.L., Peterson, R.T., Shoichet, B.K., ‘Chemical informatics and target identification in a zebrafish phenotypic screenNature Chemical Biology 8 144-146 (2012)

Bagriantsev, S., Clark, K.A., Peyronnet, R., Honoré, E., and Minor, D.L., Jr., ‘Multiple modalities act through a common gate to control K2P channel function The EMBO Journal 30 3594-3606 (2011)

Findeisen, F., Tolia, A., Arant, R., Kim, E.Y., Isacoff, E.Y., and Minor, D.L., Jr., ‘Calmodulin overexpression does not alter CaV1.2 function or oligomerization state’ Channels 5 320-324 (2011)

Shaya, D., Kreir, M., Robbins, R., Wong, S., Hammon, J., Brüggemann, A., and Minor, D.L., Jr., ‘Voltage-gated sodium channel (NaV) protein dissection creates a set of functional ‘pore-only’ proteinsProc Natl Acad Sci USA 10812313-12318(2011) 

Findeisen, F. and Minor, D.L., Jr., ‘Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation’ Channels 4 28-43 (2010)

Findeisen, F. and Minor, D.L., Jr., ‘Structural basis for the differential effects of CaBP1 and calmodulin on CaV1.2 calcium-dependent inactivation’ Structure 18 1617-1631(2010)

Kim, E.Y., Rumpf, C.H., Fujiwara, Y., Van Petegem, F., Arant, R., Findeisen, F., Cooley, E.S., Isacoff, E.Y. and Minor, D.L., Jr., ‘Multiple C-terminal Tail Ca2+/CaMs regulate CaV1.2 function but do not mediate channel dimerization’ The EMBO Journal 293924-3938 (2010)

Bagriantsev, S. and Minor, D.L., Jr., ‘Small molecule-ion channel match making: A natural fit for new ASIC ligandsNeuron 68 1-3 (2010)

Kohout, S.C., Bell, S.C., Liu, L., Xu, Q., Minor, D.L., Jr., and Isacoff, E.Y., “Electrochemical coupling in the voltage‑dependent phosphatase Ci-VSP Nature Chemical Biology 6369-375 (2010) 

Minor, D.L., Jr., “Searching for interesting channels: Pairing selection and molecular evolution methods to study ion channel structure and function” Molecular Biosystems 5 802-810 (2009) PMID: 19603113 PMCID: PMC3016960

Chatelain, F.C., Gazzarrini, S., Fujiwara, Y., Arrigoni, C., Domigan, C., Ferrara, G., Pantoja, C., Thiel, G., Moroni, A., and Minor, D.L., Jr., “Selection of inhibitor-resistant viral potassium channels identifies a selectivity filter site that affects barium and amantadine block” PLoS ONE 4 (10) e7496. doi:10.1371/journal.pone.0007496 (2009)

Findeisen, F. and Minor, D.L., Jr., ‘Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation’ Journal of General Physiology 133 327-343(2009) 

Hammon, J., Palanivelu, D.V., Chen, J., Patel, C., and Minor, D.L., Jr., ‘A green fluorescent protein screen for identification of well-expressed membrane proteins’ Protein Science 18 121‑133 (2009)

Kim, E.Y., Rumpf, C.H., Fujiwara, Y., Cooley, E.S., Van Petegem, F., and Minor, D.L., Jr.,  “Structures of CaV2 Ca2+/CaM-IQ domain complexes reveal binding modes that underlie calcium-dependent inactivation and facilitation’ Structure 161455-1467 (2008)

Fujiwara, Y. and Minor, D.L., Jr., ‘X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil’ Journal of Molecular Biology 383854-870 (2008)

Van Petegem, F, Duderstadt, K.E., Clark, K.A., Wang, M., Minor, D.L., Jr., “Alanine-scanning mutagenesis defines a conserved energetic hotspot in the CaVa1 AID-CaVb interaction site that is critical for channel modulation” Structure 14 280-294 (2008)

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) PMCID: PMC3011226

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 KChIP1/Kv4.3 T1 domain complex reveals a cross-shaped octamer” Nature Structural & Molecular Biology 13 987‑995 (2006)

Tsuruda, P., Julius, D., and Minor, D.L., Jr., “Identification and characterization of a domain required for assembly of a cold-activated TRP channel” Neuron 51 201-212 (2006)

Van Petegem, F., Chatelain, F., and Minor, D.L., Jr., “Structural basis for Ca2+/calmodulin regulation of L-type calcium channels” 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) PMID: 16157278 (Preview Neuron 47 777-778, 2005)

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

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Daniel L. Minor, Ph.D.



Email

daniel.minor@ucsf.edu

Phone

415-514-2551

Office Address

UCSF MC 3122
555 Mission Bay Blvd South
CVRI, room 452Z
San Francisco, CA 94158

Other Websites

Biomedical Sciences Graduate Program

Lab Website

PIBS