K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions. Lolicato, M., Natale, A.M., Abderemane-Ali, F., Crottes, D., Capponi, S., Duman, R. Wagner, A., Rosenberg, J.M., Grabe, M., Minor, D.L. Jr., Science Advances 6 eabc9174 (2020)
Polynuclear Ruthenium Amines Inhibit K2P Channels via a "Finger in the Dam" Mechanism. Pope, L., Lolicato, M., Minor, D.L. Jr., Cell Chemical Biology 27, 511-524 (2020)
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) 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)
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)
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
Protein and chemical determinants of BL-1249 action and selectivity for K2P channels. Pope. L., Arrigoni, C., Lou, H., Bryant, C. Gallardo-Gadoy, A., Renslo, A.R., and Minor, D.L. Jr., ACS Chemical Neuroscience 9 3153-3165, (2018)
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
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)
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)
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.
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.