Home of the Electrosome

THE MINOR LAB

Home of the Electrosome We run on electricity.

Bioelectricity made by ion channel proteins drives our thoughts, feelings, and actions. These complex macromolecular devices give the spark to life by controlling the passage of ions across cell membranes in nerves, muscles, and the brain. Our laboratory focuses on using functional, chemical, and structural approaches to uncover the molecular mechanisms by which diverse types of ion channels work, to develop new reagents that can manipulate ion channel function, and to understand the molecular mechanisms by which organisms resist toxins that target ion channels. We are particularly interested in ion channels that respond to physical forces and that are important in pain and sensory physiology.

Latest Publications

Structure of the saxiphilin:saxitoxin (STX)complex reveals a convergent molecular recognition strategy for paralytic toxins. Yen, T.-J., Lolicato, M., Thomas-Tran, R., Du Bois, J., and Minor, D.L. Jr., Science Advances 5 eaax2650 (2019) PMID: 31223657 PMCID: PMC6584486 View Press

SARAF luminal domain structure reveals a novel domain-swapped β-sandwich fold important for SOCE modulation. Kimberlin, C.R.,Meshcheriakova, A., Palty, R., Karbat, I., Reuveny, E., and Minor, D.L. Jr. Journal of Molecular Biology 431 2869-2883 (2019) PMID:31082439 PMCID: PMC6599547

A selectivity filter gate controls voltage gated calcium channel (CaV) calcium-dependent inactivation. Abderemane-Ali, F., Findeisen, F., Rossen, N.D., and Minor, D.L. Jr., Neuron 101 1134-1149 (2019) PMID: 30733149 PMCID.

Structural basis for activity and specificity of an anticoagulant anti-FXIa monoclonal antibody and a reversal agent. Ely, L., Lolicato, M. David, T., Lowe, K., Kim, Y.C., Samuel, D., Bessette, P., Garcia, J.L., Mikita, T., Minor, D.L. Jr., Coughlin, S.R., Structure 26187-198 (2018) 

A Calmodulin C-Lobe Ca2+-Dependent Switch Governs Kv7 Channel Function. Chang, A., Abderemane-Ali, F., Hura, G.L., Rossen, N.D., Gate, R.E., Minor, D.L., Jr., Neuron 97 836-852 (2018) View Video Abstract

Global versus local mechanisms of temperature sensing in ion channels. Arrigoni, C. and Minor, D.L. Jr., Pflügers Archiv: European Journal of Physiology 470 733-744 (2018) PMID: 29340775 PMCID: PMC5945320

Cryo-EM structures of the TMEM16A calcium-activated chloride channel. Dang S., Feng S., Tien J., Peters C.J., Bulkley D., Lolicato M., Zhao J., Zuberbühler K., Ye W., Qi L., Chen T., Craik C.S., Nung Jan Y., Minor D.L. Jr, Cheng Y., Yeh Jan L., Nature 552 426-429 (2017)

K2P2.1(TREK-1):activator complexes reveal a cryptic selectivity filter binding site. Lolicato, M., Arrigoni, C., Mori, T., Sekioka, Y., Bryant, C., Clark, K.A., Minor, D.L., Jr., Nature 547 364-368 (2017)

Stapled voltage-gated calcium channel (CaV) α-Interaction Domain (AID) peptides act as selective protein-protein interaction inhibitors of CaV Function. Findeisen, F., Campiglio, M., Jo, H., Abderemane-Ali, F., Rumpf, C.H., Pope, L., Rossen, N.D., Flucher, B.E., DeGrado, W.F., and Minor D.L., Jr., ACS Chemical Neuroscience 8 1313-1326 (2017)

Unfolding of a temperature-sensitive domain controls voltage-gated channel activation.  Arrigoni, C., Rohaim, A., Shaya, D., Findeisen, F., Stein, R.A. Nurva, S.R., Mishra, S., Mchaourab, H.S., and Minor, D.L., Jr., Cell 164 922-936 (2016) 

PRESS
Journal of Molecular Biology
Minor Lab Covers

MINOR LAB RESEARCH

Our lab employs a range of biochemical, biophysical, structural, and chemical biology approaches to examine the molecular structures and functions of various classes of ion channels including members of the voltage-gated potassium, voltage-gated calcium, voltage-gated sodium, and K2P channel families. Our research relies heavily on X-ray crystallography, cryo-electron microscopy, isothermal titration calorimetry, circular dichroism, and other biophysical methods. Because ion channel structure is intimately tied to function, an equally crucial part of our efforts implements structure-based tests of ion channel function using electrophysiological recordings in live cells.
Because most channels suffer from poor pharmacological profiles that limit the ability to connect ion channel genes with their physiological functions, our lab also has a strong effort to develop novel ion channel modulators. The development of new selective inhibitors and activators of channel function should provide new tools for ion channel research and may lead to the development of novel, ion channel directed pharmaceuticals.

Ion channels are the targets of many naturally occurring small molecule toxins such as saxitoxin (STX), the paralytic agent produced by oceanic ‘red tide’ blooms. The mechanisms by which animals that carry or regularly encounter such toxins resist poisoning remain poorly understood. In parallel with our interest in ion channels, we seek to uncover the molecular mechanisms of toxin resistance conferred by toxin binding proteins that act as ‘molecular sponges’ that neutralize the toxin such as STX by sequestration. Understanding the basic rules for how proteins recognize STX and other toxins should aid in the development of new means to detect and neutralize such toxins.  

Transformation

MINOR LAB LIFE

The Minor lab is located in the Smith Cardiovascular Research Building at the UCSF Mission Bay Campus in San Francisco. If you are interested in joining us, please see here.

Affiliate UCSF Graduate Programs