Divergent mechanisms of steroid inhibition in the human ρ1 GABA(A) receptor
Nature Communications 15(1): 7795, 2024
Rebecca J Howard, PhD
Biochemist
- Email: moc.liamg@drawohaber
- Web: rebahoward.net
- Print-friendly: résumé
Publications
Symmetry-adapted Markov state models of closing, opening, and desensitizing in α7 nicotinic acetylcholine receptors
Nature Communications 15(1): 9022, 2024
Zhuang Y, Howard RJ, Lindahl E
MDverse: shedding light on the dark matter of molecular dynamics simulations
eLife 12: RP90061, 2024
Tiemann JKS°, Szczuka M, Bouarroudj L, Oussaren M, Garcia S, Howard RJ, Delemotte L, Lindahl E, Baaden M, Lindorff-Larsen K, Chavent M°, Poulain P°
Allosteric cholesterol site in glycine receptors characterized through molecular simulations
Journal of Physical Chemistry B 128(20): 4996–5007, 2024
Jalalypour F, Howard RJ, Lindahl E
Functional and structural insights into activation of TRPV2 by weak acids
EMBO Journal 43: 2264–2290, 2024
Haug FM*, Pumroy RA*, Sridhar A, Pantke S, Dimek F, Fricke TC, Hage A, Herzog C, Echtermeyer FG, de la Roche J, Koh A, Kotecha A, Howard RJ, Lindahl E, Moiseenkova-Bell V, Leffler A
Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM
eLife 12: RP86016, 2024
Bergh C, Rovšnik U, Howard RJ, Lindahl E
Interactive computational and experimental approaches improve the sensitivity of periplasmic binding protein-based nicotine biosensors for measurements in biofluids
Protein Engineering, Design and Selection 37: gzae003, 2024
Haloi N*, Huang S*, Nichols AN, Fine EJ, Marotta CB, Dougherty DA, Lindahl E, Howard RJ, Mayo SL, Lester HA
tRNA shape is an identity element for an archaeal pyrrolysyl-tRNA synthetase from the human gut
Nucleic Acids Research 52(2): 513–524, 2024
Krahn N*, Zhang J*, Melnikov SV, Tharp JM, Villa A, Patel A, Howard RJ, Gabir H, Patel TR, Stetefeld J, Puglisi J, Söll D
Structure and dynamics of differential ligand binding in the human ρ-type GABA(A) receptor
Neuron 111(21): P3450–3464.E5, 2023
Cowgill J*, Fan C*, Haloi N, Tobiasson V, Zhuang Y, Howard RJ°, Lindahl E°
Structural insights into opposing actions of neurosteroids on GABA(A) receptors
Nature Communications 14: 5091, 2023
Legesse DH, Fan C, Teng J, Zhuang Y, Howard RJ, Noviello CM, Lindahl E°, Hibbs RE°
Automated simulation-based membrane-protein refinement into cryo-EM data
Biophysical Journal 122(13): P2773–2781, 2023
Yvonnesdotter L, Rovšnik U, Blau C, Lycksell M, Howard RJ, Lindahl E
Structural elucidation of ivermectin binding to α7nAChR and the induced channel desensitization
ACS Chemical Neuroscience 14(6): 1156–1165, 2023
Bondarenko V, Chen Q, Singewald K, Haloi N, Tillman TS, Howard RJ, Lindahl E, Xu Y, Tang P
An α-π transition in S6 shapes the conformational cycle of the bacterial sodium channel NavAb
Journal of General Physiology 155(2): e202213214, 2023
Choudhury K, Howard RJ, Delemotte L
Biophysical characterization of calcium-binding and modulatory-domain dynamics in a pentameric ligand-gated ion channel
Proceedings of the National Academy of Sciences of the USA 119(50): e2210669119, 2022
Lycksell M*, Rovšnik U*, Hanke A, Martel A, Howard RJ, Lindahl E
Differential interactions of resting, activated, and desensitized states of the α7 nicotinic acetylcholine receptor with lipidic modulators
Proceedings of the National Academy of Sciences of the USA 119(43): e2208081119, 2022
Zhuang Y, Noviello CM, Hibbs RE, Howard RJ, Lindahl E
Structural and dynamic mechanisms of GABA(A) receptor modulators with opposing activities
Nature Communications 13: 4582 , 2022
Zhu S, Sridhar A, Teng J, Howard RJ, Lindahl E, Hibbs RE
Probing effects of the SARS-CoV-2 E protein on membrane curvature and intracellular calcium
Biochimica et Biophysica Acta - Biomembranes 1864(10): 183994 , 2022
Mehregan A, Pérez-Conesa S, Zhuang Y, Elbahnsi A, Pasini D, Lindahl E, Howard RJ°, Ulens C°, Delemotte L°
An open state of a voltage-gated sodium channel involving a π-helix and conserved pore-facing asparagine
Biophysical Journal 121(1): P11–22, 2022
Choudhury K, Kasimova M, McComas S, Howard RJ, Delemotte L
A missense mutation converts the Na+,K+-ATPase into an ion channel and causes therapy-resistant epilepsy
Journal of Biological Chemistry 297(6): 101355, 2021
Ygberg S*, Akkuratov EE*, Howard RJ, Taylan F, Jans DC, Mahato DR, Katz A, Kinoshita PF, Portal B, Nennesmo I, Lindskog M, Karlish SJD, Andersson M, Lindstrand A°, Brismar H°, Aperia A°
Markov state models of proton- and pore-dependent activation in a pentameric ligand-gated ion channel
eLife 10: e68369, 2021
Bergh C, Heusser SA, Howard RJ, Lindahl E
Probing solution structure of the pentameric ligand-gated ion channel GLIC by small-angle neutron scattering
Proceedings of the National Academy of Sciences of the USA 118(37): e2108006118, 2021
Lycksell M, Rovšnik U, Bergh C, Johansen NT, Martel A, Porcar L, Arleth L, Howard RJ, Lindahl E
Elephants in the dark: insights and incongruities in pentameric ligand-gated ion channel models
Journal of Molecular Biology 433(17): 167128, 2021
Howard RJ
Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations
Life Science Alliance 4(8): e202101011, 2021
Rovšnik U, Zhuang Y, Forsberg BO, Carroni M, Yvonnesdotter L, Howard RJ, Lindahl E
Regulation of a pentameric ligand-gated ion channel by a semi-conserved cationic-lipid binding site
Journal of Biological Chemistry 297(2): 100899, 2021
Sridhar A*, Lummis SCR*, Pasini D, Mehregan A, Brams M, Kambara K, Bertrand D, Lindahl E, Howard RJ°, Ulens C°
Molecular dynamics simulations of ion channels
Trends in Biochemical Sciences 46(7): 621–622, 2021
Carnevale V*, Delemotte L*, Howard RJ*
Direct detection of SARS-CoV-2 using non-commercial RT-LAMP reagents on heat-inactivated samples
Scientific Reports 11: 1820, 2021
Alekseenko A*, Barrett D*, Pareja-Sanchez Y*, Howard RJ, Strandback E, Ampah-Korsah H, Rovšnik U, Zuniga-Veliz S, Klenov A, Malloo J, Ye S, Liu X, Reinius B, Elsässer S, Nyman T, Sandh G, Yin X, Pelechano V
Arrangement and symmetry of the fungal E3BP-containing core of the pyruvate dehydrogenase complex
Nature Communications 11: 4667, 2020
Forsberg BO, Aibara S, Howard RJ, Mortezaei N, Lindahl E
Shared structural mechanisms of general anaesthetics and benzodiazepines
Nature 585: 303 – 308, 2020
Kim JJ, Gharpure A, Teng J, Zhuang Y, Howard RJ, Zhu S, Noviello CM, Walsh RM, Lindahl E, Hibbs RE
Structural basis for allosteric transitions of a multidomain pentameric ligand-gated ion channel
Proceedings of the National Academy of Sciences of the USA 117(24): 13437 – 13446, 2020
Hu H, Howard RJ, Bastolla U, Lindahl E, Delarue M
Agonist selectivity and ion permeation in the α3β4 ganglionic nicotinic receptor
Neuron 104(3): 501 – 511.E6, 2019
Gharpure A, Teng J, Zhuang Y, Noviello CM, Walsh RM, Cabuco R, Howard RJ, Zaveri NT, Lindahl E, Hibbs RE
Sharing data from molecular simulations
Journal of Chemical Information and Modeling 59(10): 4093 – 4099, 2019
Abraham M, Apostolov R, Barnoud J, Bauer P, Blau C, Bonvin AMJJ, Chavent M, Chodera J, Čondić-Jurkić K, Delemotte L, Grubmüller H, Howard RJ, Jordan EJ, Lindahl E, Ollila OHS, Selent J, Smith DGA, Stansfeld PJ, Tiemann JKS, Trellet M, Woods C, Zhmurov A
Allosteric potentiation of a ligand-gated ion channel is mediated by access to a deep membrane-facing cavity
Proceedings of the National Academy of Sciences of the USA 115(42): 10672 – 10677, 2018
Heusser SA, Lycksell M, Wang X, McComas S, Howard RJ, Lindahl E
Structural basis for a bimodal allosteric mechanism of general anesthetic modulation in pentameric ligand-gated ion channels
Cell Reports 23(4): 993 - 1004, 2018
Fourati Z*, Howard RJ*, Heusser SA, Hu H, Ruza RR, Sauguet L, Lindahl E, Delarue M
Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport
Biochimica et Biophysica Acta - Biomembranes 1860(4): 927 – 942, 2018
Howard RJ°, Carnevale V°, Delemotte L°, Hellmich UA°, Rothberg BS°
Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel
Journal of Neurochemistry 138(2): 243 – 253, 2016
Heusser SA, Yoluk Ö, Klement G, Riederer EA, Lindahl E, Howard RJ
Ethanol modulation is quantitatively determined by the transmembrane domain of human α1 glycine receptors
Alcoholism: Clinical & Experimental Research 39(6): 962 – 968, 2015
Horani S, Stater EP, Corringer P-J, Trudell JR, Harris RA, Howard RJ
Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and anesthetics
Pharmacological Reviews 66(2): 396 – 412, 2014
Howard RJ, Trudell JR, Harris RA
Functional validation of virtual screening for novel agents with general anesthetic action at ligand-gated ion channels
Molecular Pharmacology 84(5): 670 – 678, 2013
Heusser SA, Howard RJ, Borghese CM, Cullins MA, Brömstrup T, Lee US, Lindahl E, Carlsson J, Harris RA
Inhibition versus potentiation of ligand-gated ion channels can be altered by a single mutation that moves ligands between intra- and intersubunit sites
Structure 21(8): 1307 - 1316, 2013
Brömstrup T, Howard RJ, Trudell JR, Harris RA, Lindahl E
Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel
Nature Communications 4: 1697, 2013
Sauguet L*, Howard RJ*, Malherbe L, Lee US, Corringer P-J, Harris RA, Delarue M
Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia crysanthemi ligand-gated ion channel (ELIC)
Journal of Biological Chemistry 288(12): 8355 – 8364, 2013
Spurny R, Billen B, Howard RJ, Brams M, Debaveye S, Price K, Weston D, Strelkov S, Tytgat J, Bertrand S, Bertrand D, Lummis S, Ulens C
Molecular mechanism for the dual alcohol modulation of Cys-loop receptors
PLoS Computational Biology 8(10): e1002710, 2012
Murail S, Howard RJ, Broemstrup T, Bertaccini EJ, Harris RA, Trudell JR, Lindahl E
The TM2 6′ position of GABA(A) receptors mediates alcohol inhibition
Journal of Pharmacology & Experimental Therapeutics 340(2): 445 – 456, 2012
Johnson WD, Howard RJ, Trudell JR, Harris RA
Structural basis for alcohol modulation of a pentameric ligand-gated ion channel
Proceedings of the National Academy of Sciences of the USA 108(29): 12149 – 12154, 2011
Howard RJ, Murail S, Ondricek KE, Corringer P-J, Lindahl E, Trudell JR, Harris RA
Alcohol binding sites in distinct brain proteins: the quest for atomic level resolution
Alcoholism: Clinical & Experimental Research 35(9): 1561 – 1573, 2011
Howard RJ, Slesinger PA, Davies DL, Das J, Trudell JR, Harris RA
Structural insight into KCNQ (Kv7) channel assembly and channelopathy
Neuron 53(5): 663 – 675, 2007
Howard RJ, Clark KA, Holton JM, Minor DL
The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1
Molecular Cell 12(6): 1427 – 1437, 2003
Walden H, Podgorski MS, Huang DT, Miller DW, Howard RJ, Minor DL, Holton JM, Schulman BA
Ring-closing metathesis of olefinic peptides: design, synthesis, and structural characterization of macrocyclic helical peptides
Journal of Organic Chemistry 66(16): 5291 – 5302, 2001
Blackwell HE, Sadowsky JD, Howard RJ, Sampson JN, Chao JA, Steinmetz WE, O’Leary DJ, Grubbs RH
*Equal contributions; °Co-corresponding authors
Preprints
Resolving the conformational ensemble of a membrane protein by integrating small-angle scattering with AlphaFold
bioRxiv 2024.09.05.611464, 2024 (preprint)
Eriksson Lidbrink S, Howard RJ, Haloi N°, Lindahl E°
Cryo-EM structures of ρ1 GABA(A) receptors with antagonist and agonist drugs
bioRxiv 2024.07.30.605774, 2024 (preprint)
Fan C°, Cowgill J, Howard RJ°, Lindahl E°
Adaptive sampling-based structural prediction reveals opening of a GABA(A) receptor through the αβ interface
bioRxiv 2024.05.03.592340, 2024 (preprint)
Haloi N, Howard RJ, Lindahl E
Vestibular modulation by stimulant derivatives in a pentameric ligand-gated ion channel
bioRxiv 2024.05.02.592243, 2024 (preprint)
Karlsson E, Andén O, Fan C, Fourati Z, Haouz A, Zhuang Y, Howard RJ°, Delarue M°, Lindahl E°
Constant-pH molecular dynamics simulations of closed and open states of a proton-gated ion channel
bioRxiv 2023.11.30.569372, 2023 (preprint)
Jansen A, Bauer P, Howard RJ, Hess B, Lindahl E
Discovering cryptic pocket opening and binding of a stimulant derivative in a vestibular site of the 5-HT(3A) receptor
bioRxiv 2023.11.13.566806, 2023 (preprint)
Haloi N, Karlsson E, Delarue M, Howard RJ, Lindahl E
Selected Talks
Potentiation of ligand-gated ion channels by stimulant derivatives via a vestibular binding site
Chicago, IL 2024
Structure and dynamics of differential ligand binding in the human ρ-type GABA(A) receptor
Philadelphia, PA 2024
Structural dynamics of subtype-specific pharmacology in human GABA(A) receptors
St Louis, MO 2023
Washington University in St Louis Anesthesiology Seminar Series
Structure-function studies of alcohol-sensitive ligand-gated ion channels from the periphery
Volterra, Italy 2023
An open state of a voltage-gated sodium channel involving a π-helix and conserved pore-facing asparagine
San Diego, CA 2023
Convergent mechanisms from simulations and structure-function studies of model pentameric ligand-gated ion channels
South Hadley, MA 2022
Structure and dynamics of conserved modulatory mechanisms in a pentameric ligand-gated ion channel
Ottawa, Canada 2022
Differential interactions of closed, open, and desensitized states of the α7 nicotinic acetylcholine receptor with lipidic modulators
San Francisco, CA 2022
Open state of bacterial sodium channel: insights from molecular dynamics simulations
San Francisco, CA 2022
Transmembrane mechanisms of allosteric modulation in pentameric ion channels: from bacteria to brain
Austin, TX 2020 (remote)
Dissecting dynamics of multi-site allostery in a pentameric ligand-gated ion channel
Roscoff, France 2019
Conférences Jacques Monod: Ligand-gated ion channels from atomic structure to synaptic transmission
Anesthetic modulation via transmembrane interfacial sites in a pentameric ligand-gated ion channel
Stockholm, Sweden 2018
Understanding the molecular basis for general anesthesia through structure, function, and modeling
Tokyo, Japan 2018
Allosteric modulation via an intersubunit transmembrane site in Cys-loop receptors
Kyoto, Japan 2018
International Society for Biomedical Research on Alcoholism
Allosteric mechanisms of anesthetic modulation of pentameric ligand-gated ion channels
Chicago, IL 2018
Structural details of an allosteric mechanism for bimodal anesthetic modulation of pentameric ligand-gated ion channels
San Francisco, CA 2018
Multi-site allosteric modulation by general anesthetics revealed by structural, functional, and computational studies in a model pentameric ligand-gated ion channel
Tällberg, Sweden 2017
Selective spirits: Physicochemical determinants for alcohol modulation of ligand-gated ion channels
Berlin, Germany 2016
Alcohol at the interface: Functional and computational insights from prokaryotic Cys-loop receptors
New Orleans, LA 2016
Alcohol at the interface: Structural insights from model Cys-loop receptors
Austin, TX 2016
Swimming to a small pond: Biochemistry at a liberal arts college
Austin, TX 2015
Too much of a good thing: Evolving our relationship with alcohol
Saratoga Springs, NY 2014
Alcohol binding to ligand-gated ion channels revealed in a prokaryotic model system
Portland, ME 2013
Alcohol modulation of ligand-gated ion channels: Insights and opportunities from new structures
Stockholm, Sweden 2013
Structural sites of alcohol modulation in ligand-gated ion channels
Canberra, Australia 2013
Simple structural models for alcohol modulation of ligand-gated ion channels
Albany, NY 2012
Modeling alcohol modulation of brain targets using homologous proteins from lower organisms
Sapporo, Japan 2012
Structural basis for alcohol modulation of a bacterial ligand-gated ion channel
San Francisco, CA 2012
A combined functional-computational approach to characterizing structural sites of anesthetic modulation
San Diego, CA 2012
Structural basis for alcohol modulation of pentameric ligand-gated ion channels
San Francisco, CA 2012
Structural basis for alcohol modulation of a pentameric ligand-gated ion channel
Stockholm, Sweden 2011
Sites of alcohol modulation of TRPV1 channels
San Antonio, TX 2010
Structural insight into KCNQ channel assembly and channelopathy
San Jose del Cabo, Mexico 2006