Daniel Minor, PhD | Neuroscience Graduate Program

Professor

M_Cardiovascular Research Inst

415-514-2551

Structural and Mechanistic Studies of Ion Channels and Ion Channel Regulation

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.

Current Projects

Structural understanding of ion channel action and regulation
Molecular evolution of ion channel modulators for channels
Membrane proteins expression and structure

Minor Lab

Publications

Author Correction: Structure of the human K2P13.1 channel reveals a hydrophilic pore restriction and lipid cofactor site.

Roy-Chowdhury S, Jang S, Abderemane-Ali F, Naughton F, Grabe M, Minor DL

A lipid plug affects K2P6.1(TWIK-2) function.

bioRxiv : the preprint server for biology

Mondal A, Niranjan S, Minor DL

CACNA1D is a circadian gene and causes familial advanced sleep phase.

Webb JM, Abderemane-Ali F, Ashbrook L, Ma M, Nibber N, Zou X, Yamazaki M, Wohler E, Sobreira N, Minor DL, Fu YH, Ptácek LJ

Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins.

Zakrzewska S, Nixon SA, Chen Z, Hajare HS, Park ER, Mulcahy JV, Arlinghaus KM, Neu E, Konovalov K, Provasi D, Leighfield TA, Filizola M, Du Bois J, Minor DL

Structure of the human K2P13.1 channel reveals a hydrophilic pore restriction and lipid cofactor site.

Roy-Chowdhury S, Jang S, Abderemane-Ali F, Naughton F, Grabe M, Minor DL

Electrosome assembly: Structural insights from high voltage-activated calcium channel (CaV)-chaperone interactions.

Chen Z, Minor DL

Development of covalent chemogenetic K2P channel activators.

Deal PE, Lee H, Mondal A, Lolicato M, Mendonça PRF, Black H, Jang S, El-Hilali X, Bryant C, Isacoff EY, Renslo AR, Minor DL

Structure of the human K2P13.1(THIK-1) channel reveals a novel hydrophilic pore restriction and lipid cofactor site.

Roy-Chowdhury S, Jang S, Abderemane-Ali F, Naughton F, Grabe M, Minor DL

Expression, purification, and characterization of anuran saxiphilins using thermofluor, fluorescence polarization, and isothermal titration calorimetry.

Chen Z, Zakrzewska S, Hajare HS, Du Bois J, Minor DL

Development of covalent chemogenetic K 2P channel activators.

Deal PE, Lee H, Mondal A, Lolicato M, de Mendonca PRF, Black H, El-Hilali X, Bryant C, Isacoff EY, Renslo AR, Minor DL

EMC chaperone-CaV structure reveals an ion channel assembly intermediate.

Chen Z, Mondal A, Ali FA, Jang S, Niranjan S, Montaño JL, Zaro BW, Minor DL

Structural basis for CaVa2d:gabapentin binding.

Chen Z, Mondal A, Minor DL

Selective posttranslational inhibition of CaV�1-associated voltage-dependent calcium channels with a functionalized nanobody.

Morgenstern TJ, Nirwan N, Hern?ndez-Ochoa EO, Bibollet H, Choudhury P, Laloudakis YD, Ben Johny M, Bannister RA, Schneider MF, Minor DL, Colecraft HM

Definition of a saxitoxin (STX) binding code enables discovery and characterization of the anuran saxiphilin family.

Chen Z, Zakrzewska S, Hajare HS, Alvarez-Buylla A, Abderemane-Ali F, Bogan M, Ramirez D, O'Connell LA, Du Bois J, Minor DL

Quaternary structure independent folding of voltage-gated ion channel pore domain subunits.

Arrigoni C, Lolicato M, Shaya D, Rohaim A, Findeisen F, Fong LK, Colleran CM, Dominik P, Kim SS, Schuermann JP, DeGrado WF, Grabe M, Kossiakoff AA, Minor DL

Differential effects of modified batrachotoxins on voltage-gated sodium channel fast and slow inactivation.

MacKenzie TMG, Abderemane-Ali F, Garrison CE, Minor DL, Bois JD

Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on "toxin sponge" proteins.

Abderemane-Ali F, Rossen ND, Kobiela ME, Craig RA, Garrison CE, Chen Z, Colleran CM, O'Connell LA, Du Bois J, Dumbacher JP, Minor DL

Inroads into membrane physiology through transport nanomachines.

Stockbridge RB, Gaudet R, Grabe M, Minor DL

Ion channels: Intersection of Structure, Function, and Pharmacology.

Moiseenkova-Bell V, Delemotte L, Minor DL

Structural insights into the mechanisms and pharmacology of K2P potassium channels.

Natale AM, Deal PE, Minor DL

Production of K2P2.1 (TREK-1) for structural studies.

Lee H, Lolicato M, Arrigoni C, Minor DL

Preface.

Minor DL, Colecraft HM

The Polysite Pharmacology of TREK K2P Channels.

Pope L, Minor DL

K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.

Lolicato M, Natale AM, Abderemane-Ali F, Crottès D, Capponi S, Duman R, Wagner A, Rosenberg JM, Grabe M, Minor DL

Polynuclear Ruthenium Amines Inhibit K2P Channels via a "Finger in the Dam" Mechanism.

Pope L, Lolicato M, Minor DL

Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins.

Yen TJ, Lolicato M, Thomas-Tran R, Du Bois J, Minor DL

SARAF Luminal Domain Structure Reveals a Novel Domain-Swapped ß-Sandwich Fold Important for SOCE Modulation.

Kimberlin CR, Meshcheriakova A, Palty R, Raveh A, Karbat I, Reuveny E, Minor DL

A Selectivity Filter Gate Controls Voltage-Gated Calcium Channel Calcium-Dependent Inactivation.

Abderemane-Ali F, Findeisen F, Rossen ND, Minor DL

Protein and Chemical Determinants of BL-1249 Action and Selectivity for K2P Channels.

Pope L, Arrigoni C, Lou H, Bryant C, Gallardo-Godoy A, Renslo AR, Minor DL

A Calmodulin C-Lobe Ca2+-Dependent Switch Governs Kv7 Channel Function.

Chang A, Abderemane-Ali F, Hura GL, Rossen ND, Gate RE, Minor DL

Global versus local mechanisms of temperature sensing in ion channels.

Arrigoni C, Minor DL

Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa Monoclonal Antibody and a Reversal Agent.

Ely LK, Lolicato M, David T, Lowe K, Kim YC, Samuel D, Bessette P, Garcia JL, Mikita T, Minor DL, Coughlin SR

Cryo-EM structures of the TMEM16A calcium-activated chloride channel.

Dang S, Feng S, Tien J, Peters CJ, Bulkley D, Lolicato M, Zhao J, Zuberbühler K, Ye W, Qi L, Chen T, Craik CS, Jan YN, Minor DL, Cheng Y, Jan LY

Channel surfing uncovers a dual-use transporter.

Minor DL

K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site.

Lolicato M, Arrigoni C, Mori T, Sekioka Y, Bryant C, Clark KA, Minor DL

Stapled Voltage-Gated Calcium Channel (CaV) a-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of CaV Function.

Findeisen F, Campiglio M, Jo H, Abderemane-Ali F, Rumpf CH, Pope L, Rossen ND, Flucher BE, DeGrado WF, Minor DL

Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.

M_Anatomy-General

Arrigoni C, Rohaim A, Shaya D, Findeisen F, Stein RA, Nurva SR, Mishra S, Mchaourab HS, Minor DL

Let It Go and Open Up, an Ensemble of Ion Channel Active States.

M_Anatomy-General

Minor DL

Insights into the molecular foundations of electrical excitation.

Gaudet R, Roux B, Minor DL

Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels.

Lolicato M, Riegelhaupt PM, Arrigoni C, Clark KA, Minor DL

Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart.

Payandeh J, Minor DL

Tethered protein display identifies a novel Kir3.2 (GIRK2) regulator from protein scaffold libraries.

Bagriantsev SN, Chatelain FC, Clark KA, Alagem N, Reuveny E, Minor DL

Conduits of life's spark: a perspective on ion channel research since the birth of neuron.

Isacoff EY, Jan LY, Minor DL

Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels.

Shaya D, Findeisen F, Abderemane-Ali F, Arrigoni C, Wong S, Nurva SR, Loussouarn G, Minor DL

Apo states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain.

Findeisen F, Rumpf CH, Minor DL

A high-throughput functional screen identifies small molecule regulators of temperature- and mechano-sensitive K2P channels.

Bagriantsev SN, Ang KH, Gallardo-Godoy A, Clark KA, Arkin MR, Renslo AR, Minor DL

Patch-clamp characterization of the MscS-like mechanosensitive channel from Silicibacter pomeroyi.

Petrov E, Palanivelu D, Constantine M, Rohde PR, Cox CD, Nomura T, Minor DL, Martinac B

Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC).

Tien J, Lee HY, Minor DL, Jan YN, Jan LY

Using yeast to study potassium channel function and interactions with small molecules.

Bagriantsev SN, Minor DL

Structure of a Ca(2+)/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M current modulation.

Xu Q, Chang A, Tolia A, Minor DL

Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains.

Bagriantsev SN, Clark KA, Minor DL

A glutamate switch controls voltage-sensitive phosphatase function.

Liu L, Kohout SC, Xu Q, Müller S, Kimberlin CR, Isacoff EY, Minor DL

Chemical informatics and target identification in a zebrafish phenotypic screen.

Laggner C, Kokel D, Setola V, Tolia A, Lin H, Irwin JJ, Keiser MJ, Cheung CY, Minor DL, Roth BL, Peterson RT, Shoichet BK

Multiple modalities converge on a common gate to control K2P channel function.

Bagriantsev SN, Peyronnet R, Clark KA, Honoré E, Minor DL

Voltage-gated sodium channel (NaV) protein dissection creates a set of functional pore-only proteins.

Shaya D, Kreir M, Robbins RA, Wong S, Hammon J, Brüggemann A, Minor DL

Calmodulin overexpression does not alter Cav1.2 function or oligomerization state.

Findeisen F, Tolia A, Arant R, Kim EY, Isacoff E, Minor DL

Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.

Findeisen F, Minor DL

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.

Minor DL, Findeisen F

Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.

Kim EY, Rumpf CH, Van Petegem F, Arant RJ, Findeisen F, Cooley ES, Isacoff EY, Minor DL

Small molecule ion channel match making: a natural fit for new ASIC ligands.

Bagriantsev SN, Minor DL

Electrochemical coupling in the voltage-dependent phosphatase Ci-VSP.

Kohout SC, Bell SC, Liu L, Xu Q, Minor DL, Isacoff EY

Selection of inhibitor-resistant viral potassium channels identifies a selectivity filter site that affects barium and amantadine block.

Chatelain FC, Gazzarrini S, Fujiwara Y, Arrigoni C, Domigan C, Ferrara G, Pantoja C, Thiel G, Moroni A, Minor DL

Crystal structure of a trimeric form of the K(V)7.1 (KCNQ1) A-domain tail coiled-coil reveals structural plasticity and context dependent changes in a putative coiled-coil trimerization motif.

Xu Q, Minor DL

Searching for interesting channels: pairing selection and molecular evolution methods to study ion channel structure and function.

Minor DL

Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation.

Findeisen F, Minor DL

2007 annual progress report synopsis of the Center for Structures of Membrane Proteins.

Stroud RM, Choe S, Holton J, Kaback HR, Kwiatkowski W, Minor DL, Riek R, Sali A, Stahlberg H, Harries W

A green fluorescent protein screen for identification of well-expressed membrane proteins from a cohort of extremophilic organisms.

Hammon J, Palanivelu DV, Chen J, Patel C, Minor DL

Structures of CaV2 Ca2+/CaM-IQ domain complexes reveal binding modes that underlie calcium-dependent inactivation and facilitation.

Kim EY, Rumpf CH, Fujiwara Y, Cooley ES, Van Petegem F, Minor DL

X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil.

Fujiwara Y, Minor DL

Transmembrane domain length of viral K+ channels is a signal for mitochondria targeting.

Balss J, Papatheodorou P, Mehmel M, Baumeister D, Hertel B, Delaroque N, Chatelain FC, Minor DL, Van Etten JL, Rassow J, Moroni A, Thiel G

Alanine-scanning mutagenesis defines a conserved energetic hotspot in the CaValpha1 AID-CaVbeta interaction site that is critical for channel modulation.

Van Petegem F, Duderstadt KE, Clark KA, Wang M, Minor DL

Puzzle plugged by protein pore plasticity.

Minor DL

The neurobiologist's guide to structural biology: a primer on why macromolecular structure matters and how to evaluate structural data.

Minor DL

Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex.

Van Petegem F, Chatelain FC, Minor DL

The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1.

Walden H, Podgorski MS, Huang DT, Miller DW, Howard RJ, Minor DL, Holton JM, Schulman BA

Consensus-derived structural determinants of the ankyrin repeat motif.

Mosavi LK, Minor DL, Peng ZY