Selected Publications

Kschonsak et al., ”Structural architecture of the human NALCN channelosome”, 2022, Nature

Braun et al., ”High-throughput characterization of photocrosslinker-bearing ion channel variants to map residues critical for function and pharmacology”, 2021, PLoS Biology

Galleano & Harms et al., ”Functional crosstalk between phosphorylation and disease-causing mutations in the cardiac sodium channel Nav1.5”, 2021, PNAS

Khoo & Galleano et al., ”Chemical modification of proteins by insertion of synthetic peptides using tandem protein trans-splicing”, 2020, Nature Communications

Borg & Braun et al., “Mechanism and site of action of big dynorphin on ASIC1a”, 2020, PNAS

Chua et al., “The NALCN sodium leak channel complex is modulated by voltage and calcium”, 2020, Science Advances

Left: Top down view of a Cys-loop receptor



Schott, K., Usher, S.G., Serra, O., Carnevale, E., Pless, S.A., Chua, H.C., ”Unplugging lateral fenestrations of NALCN reveals a hidden drug binding site within the pore regionPNAS [PubMed

Magni, L., Yu, H., Christensen, N.M., Poulsen, M.H. (…), Pless, S.A., Jørgensen, N.R., Nowak, I., ”Human P2X7 receptor variants Gly150Arg and Arg276His have differential effects on risk association and cellular functions in pancreatic cancerCancer Cell International [PubMed]

Holm, C. M.*, Topaktas, A.B.*, Dannesboe, J., Pless, S.A., Heusser, S.A., ”Dynamic conformational changes of acid-sensing ion channels in different desensitizing conditions;  * = co-first, Biophyscial Journal [bioRxiv] [PubMed]


Sarkar, D.*, Galleano, I.*, Heusser, S.A., Ou, S.Y., Uzun, G.R., Khoo, K.K., van Noort, G.J.v.d.H., Harrison, J.S., Pless, S.A., ”Protein semisynthesis underscores role of a conserved lysine in activation and desensitization of acid-sensing ion channels”; * = co-first, Cell Chemical Biology [bioRxiv] [PubMed]


Noland, C.L.*, Chua, H.C.*, Kschonsak, M.*, Heusser, S.A., Braun, N., Chang, T., Tam, C., Tang, J., Arthur, C.P., Ciferri, C.*, Pless, S.A.*, Payandeh, J.*, “Structure-guided unlocking of Nax reveals a non-selective tetrodotoxin-sensitive cation channel”; * = co-first/-corresponding, Nature Communications [Link]

Gasparri, F.*, Sarkar, D.*, Bielickaite, S., Poulsen, M.H., Hauer, A.S.*, Pless, S.A.*, ”P2X2 receptor subunit interfaces are missense variant hotspots where mutations tend to increase apparent ATP affinity”; * = co-first/-corresponding, British Journal of Pharmacology [bioRxiv] [PubMed]

Heusser, S.A.*, Borg, C.B.*, Colding, J.M., Pless, S.A., ”Conformational decoupling in acid-sensing ion channels uncovers mechanism and stoichiometry of PcTx1-mediated inhibition”; * = equal contribution; eLife  [bioRxiv]  [PubMed]

Kschonsak, M., Chua, H.C., Weidling, C.*, Chakouri, N.*, Noland, C.L.*, Schott, K., Chang, T., Tam, C., Patel, N., Arthur, C., Leitner, A.*, Ben-Johny, M.*, Ciferri, C.*, Pless, S.A.*, Payandeh, J.*, ”Structural architecture of the human NALCN channelosome”;* = co-third/-corresponding; Nature [PubMed]


Heusser, S.A. & Pless, S.A., ”Acid-sensing ion channels as potential therapeutic targets”; Trends in Pharmacological Sciences  [PubMed]

Obergrussberger, A., (…), Braun, N, Friis, S., Pless, S.A., Fertig, N., ”The suitability of high-throughput automated patch clamp for physiological applications”; J Physiol [PubMed]

Braun, N., Friis, S., Ihling, C., Sinz, A., Andersen, J., Pless, S.A., ”High-throughput characterization of photocrosslinker-bearing ion channel variants to map residues critical for function and pharmacology”; PLoS Biology  [bioRxiv] [PubMed]

Sheikh, Z.P., Wulf, M., Friis, S., Althaus, M., Lynagh, T., Pless, S.A., ”The M1 and pre-M1 segments contribute differently to ion selectivity in ASICs and ENaCs”Journal of General Phyiology [bioRxiv]  [PubMed]

Galleano, I.*, Harms, H.*, Choudhury, K., Khoo, K.K., Delemotte, L., Pless, S.A., ”Functional crosstalk between phosphorylation and disease-causing mutations in the cardiac sodium channel Nav1.5”; * = equal contribution, PNAS, [bioRxiv] [PubMed]

Jehasse, K., (…), Chua, H.C., Pless, S.A., (…), Seutin, V., “The gating pore blocker 1-(2,4-xylyl)guanidinium selectively inhibits pacemaking of midbrain dopaminergic neurons”, Neuropharmacology[PubMed]

Sarkar, D.*, Harms, H.*, Galleano, I., Sheikh, Z.P., Pless, S.A., ”Ion channel engineering using protein trans-splicing”; * = equal contribution, Methods in Enzymology [LINK]


Lynagh, T.*, Kiontke, S., Meyhoff-Madesen, M., Gless, B.H., Johannesen, J., Kattermann, S., Christiansen, A., Dufva, M., Laustsen, A.H., Devkota, K., Olsen, C.A., Kümmerl, D., Pless, S.A., Lohse, B.*, ”Peptide inhibitors of the a-cobratoxin-nicotinic acetylcholine receptor interaction”; * = co-corresponding; Journal of Medicinal Chemistry[PubMed]

Braun, N., Sheikh, Z.P., Pless, S.A., ”The current chemical biology toolbox for studying ion channels”; The Journal of Physiology, [PubMed]

Kschonsak, M., Chua, H.C.*, Noland, C.L.*, Weidling, C.*, Clairfeuille, T., Bahlke, O.O., Ameen, A.O., Li, Z.R., Arthur, C., Ciferri, C.*, Pless, S.A.*, Payandeh, J.*, ”Structure of the human sodium leak channel NALCN”;* = co-second/-corresponding; Nature, [free access[PubMed]

Khoo, K.K.*, Galleano, I.*, Gasparri, F., Wieneke, R., Harms, H., Poulsen, M.H., Chua, H.C., Wulf, M., Tampé, R., Pless, S.A., ”Chemical modification of proteins by insertion of synthetic peptides using tandem protein trans-splicing”;* = equal contribution; Nature Communications, bioRxiv [PubMed]

Chua, H.C., Wulf, M., Weidling, C., Rasmussen, L.P., Pless, S.A.; “The NALCN sodium leak channel complex is modulated by voltage and extracellular calcium”; Science Advances; [bioRxiv] [PubMed]

Borg, C.B.*, Braun, N.*, Heusser, S.A., Bay, Y., Weis, D., Galleano, I., Lund, C., Tian, W., Haugaard-Kedström, L.M., Bennett, E.P., Lynagh, T., Strømgaard, K., Andersen, J., Pless, S.A.; “Mechanism and site of action of big dynorphin on ASIC1a”;* = equal contribution; PNAS; [bioRxiv] [PubMed]

Lynagh, T.*,  Flood, E.*,  Boiteux, C., Sheikh, Z.P., Allen, T.W.*, Pless, S.A.*; “Determinants of ion selectivity ASIC1a- and ASIC2a-containing acid-sensing ion channels”;* = equal contribution/co-corresponding; Journal of General Physiology [PubMed]


Kasimova, M.A.*, Lynagh, T.*, Sheikh, Z.P., Granata, D., Borg, C.B., Carnevale, V.*, Pless, S.A.*; “Evolutionarily conserved interactions within the pore domain of acid-sensing ion channels”; * = equal contribution/co-corresponding; Biophysical Journal[PubMed]

Pless, S.A. & Sivilotti, L.G.; “A tale of ligands big and small: an update on how pentameric ligand-gated ion channels interact with agonists and proteins”; Current Opinion in Physiology [PubMed]

Gasparri, F., Wengel, J., Grutter, T., Pless, S.A., “Molecular determinants for agonist recognition and discrimination in P2X2 receptors”, Journal of General Physiology [PubMed]


Yau, M.C., Kim, R.Y., Wang, C.K., Yang, R., Pless, S.A., Kurata, H.T., “One drug-sensitive subunit is sufficient for a near-maximal retigatibe effect in KCNQ channels”, Journal of General Physiology[PubMed]

Wang, A. W., Yau, M.C., Wang, C.K., Yang, R., Pless, S.A., Kurata, H.T., “Four drug-sensitive subunits are required for maximal effect of a voltage sensor-targeted KCNQ opener”, Journal of General Physiology[PubMed]

Sereikaitė, V., Jensen, T.M.T., Bartling, C.R.O., Jemth, P., Pless, S.A., Strømgaard, K.; “Probing backbone hydrogen bonds in proteins by amide-to-ester mutations”; ChemBioChem, [PubMed]

Lynagh, T., Mikhaleva, Y., Colding, J.M., Glover, J.C., Pless, S.A.; “Acid-sensing ion channels emerged over 600 MYA and are conserved throughout the deuterostomes”; PNAS, [PubMed]

Chua, H.C., Servatius, H., Asatryan, B., Schaller, A.,  Rieubland, C., Noti, F., Seiler, J., Roten, L., Baldinger, S.H., Tanner, H., Fuhrer, J., Haeberlin, A., Lam, A., Pless, S.A., Medeiros-Domingo, A.; “Unexplained cardiac arrest: a tale of conflicting interpretations of KCNQ1 genetic test results”; Clinical Research in Cardiology [PubMed]

Khoo, K.K. & Pless, S.A.; “How an intrinsic ligand tunes the activity of a potassium channel”; Journal of General Physiology [PubMed]

Servatius, H., Porro, A., Pless, S.A., Schaller, A., Asatryan, B., Tanner, H., de Marchi, S.F., Roten, L., Seiler, J., Haeberlin, A., Baldinger, S.H., Noti, F., Lam, A., Fuhrer, J., Moroni, A., Medeiros-Domingo, A.; “Phenotypic spectrum of HCN4 mutations”; Circulation: Genomic and Precision Medicine [PubMed]

Wulf, M. & Pless, S.A.; “High-Sensitivity Fluorometry to Resolve Ion Channel Conformational Dynamics”; Cell Reports [PubMed]

Callau-Vazquez, D., Pless, S.A., Lynagh, T.; “Investigation of agonist recognition and channel properties in a flatworm glutamate-gated chloride channel”; Biochemistry [PubMed]


Kim, R.Y., Pless, S.A., Kurata, H.T.; “PIP2 mediates functional coupling and pharmacology of neuronal KCNQ channels”; Proc Nat Acad Sci (PNAS) [PubMed]

Lynagh, T., Romero-Rojo, J.L., Lund, C., Pless, S.A.; “Molecular basis for allosteric inhibition of acid-sensing ion channel 1a by ibuprofen”; Journal of Medicinal Chemistry [PubMed]

Lynagh, T.,  Flood, E.,  Boiteux, C., Wulf, M., Komnatnyy, V.V., Colding, J.M., Allen, T.W., Pless, S.A.; “A selectivity filter at the intracellular end of the acid-sensing ion channel pore”; eLife [PubMed]

Lynagh, T., Komnatnyy, V.V., Pless, S.A.; “Unique contributions of an arginine side chain to ligand-recognition in a glutamate-gated chloride channcel”; The Journal of Biological Chemistry [PubMed]


Braun, N., Lynagh, T., Yu, R., Biggin, P.C., Pless, S.A.; “The role of an absolutely conserved tryptophan pair in the extracellular domain of Cys-loop receptors”; ACS Chemical Neuroscience [PubMed]


Pless, S.A. & Ahern, C.A.; “Applying chemical biology to ion channels”; Adv Exp Med Biol (Springer book) [PubMed]

Kim, R.Y., Yau M.C., Galpin J.D., Seebohm G., Ahern, C.A., Pless, S.A., Kurata, H.T., ; “Atomic basis for therapeutic activation of neuronal potassium channels”; Nature Communications [PubMed]

Zhang, R.S., Wright, J., Pless, S.A., Nunez, J.J., Kim, R.Y., Li, J.B., Yang, R., Ahern, C.A., Kurata, H.T., ; “A conserved residue cluster that governs kinetics of ATP-dependent gating of Kir6.2 potassium channels”; The Journal of Biological Chemistry [PubMed]

Pless, S.A., Kim, R., Ahern, C.A., Kurata, H.T., ; “Atom-by-atom engineering of voltage-gated ion channels: magnified insights into function and pharmacology”; Journal of Physiology [PubMed]


Pless, S.A.; “Caught in the act: mutliple binding sites for memantine”; Structure [PubMed]

Lynagh, T. & Pless, S.A.; “Principles of agonist recognition in Cys-loop receptors”; Frontiers in Physiology [PubMed]

Pless, S.A., Elstone, F.D., Niciforovic, A.P., Galpin, J.D., Yang, R., Kurata, H.T., Ahern, C.A.; “Asymmetric functional contributions of acidic and aromatic side chains in sodium channel voltage-sensor domains”; The Journal of General Physiology [PubMed]


Pless, S.A., Galpin, J.D., Niciforovic, A.P., Kurata, H.T., Ahern, C.A.; “Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels”; eLife [PubMed]

Pless, S.A., Niciforovic, A.P., Nunez, J.J., Galpin, J.D., Kurata, H.T., Ahern, C.A.; “A novel mechanism for fine-tuning open state stability in a voltage-gated potassium channel”; Nature Communications [PubMed]

Pless, S.A. & Ahern, C.A.; “Probing ligand receptor interactions with unnatural amino acids”; Annual Review of Pharmacology and Toxicology [PubMed]

Rivera-Aceveda, R.E., Pless, S.A., Schwarz, S.K., Ahern, C.A.; “Expression-dependent pharmacology of TRPV1 in Xenopus laevis oocytes”; Channels [PubMed]


Lacroix, J.J., Pless, S.A., Maragliano, L., Campos, F.V., Galpin, J.D., Ahern, C.A., Roux, B., Bezanilla, F.; “Intermediate state trapping of a voltage sensor”; The Journal of General Physiology [PubMed]

Rivera-Aceveda, R.E., Pless, S.A., Schwarz, S.K., Ahern, C.A.; ”Extracellular quarternary ammonium blockade of transient receptor vanilloid subtype 1 channels expressed in Xenopus laevis oocytes”; Molecular Pharmacology [PubMed]


Pless, S.A.*, Leung, A., Galpin, J.D., Ahern, C.A.; ”Contributions of conserved residues at the gating interface of glycine receptors”, *-corresponding author, The Journal of Biological Chemistry [PubMed]

Pless, S.A., Galpin, J.D., Niciforovic, A, Ahern, C.A.; “Contributions of counter charge in a potassium channel voltage sensor”, Nature Chemical Biology [PubMed]

Pless, S.A., Galpin, J.D., Frankel, A., Ahern, C.A.; “Molecular basis for inhibition of cardiac sodium channels by class Ib anti-arrythmics”; Nature Communications [PubMed]

Rivera-Aceveda, R.E., Pless, S.A., Ahern, C.A., Schwarz, S.K.; “The quaternary lidocaine derivative, QX-314, exerts biphasic effects on TRPV1 channels in vitro”, Anesthesiology [PubMed]

Pless, S.A., Hanek, A.P., Lynch, J.W., Lester, H.A., Dougherty, D.A., Lummis, S.C.; “A cation-pi interaction in the glycine receptor binding site is conserved for different agonists”, Molecular Pharmacology [PubMed]


Wang, Q., Pless, S.A., Lynch J.W.; “Ligand- and subunit-specific conformational changes in the ligand-binding domain and the TM2-TM3 linker of alpha 1, beta 2, gamma 2 GABA-A receptors”; The Journal of Biological Chemistry [PubMed]

Pless, S.A., Lynch J.W.; “The magnitude of a conformational change in the glycine receptor beta1- beta2 loop is correlated with agonist efficacy”; The Journal of Biological Chemistry [PubMed]

Pless, S.A., Lynch, J.W.; “Ligand-specific conformational changes in the alpha1 glycine receptor ligand-binding domain”; The Journal of Biological Chemistry [PubMed]

Pless, S.A., Lynch, J.W.; “Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits”; Journal of Neurochemistry [PubMed]


Pless, S.A., Millen, K.S., Hanek, A.P., Lynch, J.W., Lester, H.A., Dougherty, D.A., Lummis, S.C.; “A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue”, Journal of Neuroscience [PubMed]

Pless, S.A., Lynch, J.W.; “Illuminating the structure and function of Cys-loop receptors”; Clinical and Experimental Physiology and Pharmacology [PubMed]

Pless, S.A., Dibas, M.I., Lester, H.A., Lynch, J.W.;
“Conformational variability of the glycine receptor M2 domain in response to activation by different agonists”; The Journal of Biological Chemistry [PubMed]