Crina Nimigean, Ph.D.

Associate Professor of Physiology and Biophysics

  • Associate Professor of Physiology and Biophysics in Anesthesiology (primary appointment)
  • Associate Professor of Biochemistry

212-746-5947

525 East 68th Street, Room A-1050
New York, NY 10021


Techniques

Research Areas


Research Summary:

Ion channels are key players in many physiological processes and their function is tightly regulated. The work in the lab is targeted towards understanding how ion channel structure and mechanism interrelate at the molecular level to fulfill diverse physiological needs. In particular, we are interested in ligand-gated ion channels and their allosteric regulation and we investigate them via a combination of structural, biochemical, biophysical, and electrophysiological approaches.  We use cryo-EM to determine high-resolution structures of ion channels in different conformations and in different lipid environments that we can directly assign to functional states via information from single-channel recording and other functional assays. This will ultimately pave the way towards conformationally-selective drug therapies.

 

Recent Publications:

  1. Xu, Y, Zhang, D, Rogawski, R, Nimigean, CM, McDermott, AE. Identifying coupled clusters of allostery participants through chemical shift perturbations. Proc. Natl. Acad. Sci. U.S.A. 2019;116 (6):2078-2085. doi: 10.1073/pnas.1811168116. PubMed PMID:30679272 PubMed Central PMC6369819.
  2. Falzone, ME, Rheinberger, J, Lee, BC, Peyear, T, Sasset, L, Raczkowski, AM et al.. Structural basis of Ca2+-dependent activation and lipid transport by a TMEM16 scramblase. Elife. 2019;8 :. doi: 10.7554/eLife.43229. PubMed PMID:30648972 PubMed Central PMC6355197.
  3. Schmidpeter, PAM, Nimigean, CM. Fluorescence Titrations to Determine the Binding Affinity of Cyclic Nucleotides to SthK Ion Channels. Bio Protoc. 2018;8 (19):. doi: 10.21769/BioProtoc.3041. PubMed PMID:30417032 PubMed Central PMC6221198.
  4. Marchesi, A, Gao, X, Adaixo, R, Rheinberger, J, Stahlberg, H, Nimigean, C et al.. An iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel. Nat Commun. 2018;9 (1):3978. doi: 10.1038/s41467-018-06414-8. PubMed PMID:30266906 PubMed Central PMC6162275.
  5. Rheinberger, J, Gao, X, Schmidpeter, PA, Nimigean, CM. Ligand discrimination and gating in cyclic nucleotide-gated ion channels from apo and partial agonist-bound cryo-EM structures. Elife. 2018;7 :. doi: 10.7554/eLife.39775. PubMed PMID:30028291 PubMed Central PMC6093708.
  6. Schmidpeter, PAM, Gao, X, Uphadyay, V, Rheinberger, J, Nimigean, CM. Ligand binding and activation properties of the purified bacterial cyclic nucleotide-gated channel SthK. J. Gen. Physiol. 2018;150 (6):821-834. doi: 10.1085/jgp.201812023. PubMed PMID:29752414 PubMed Central PMC5987880.
  7. Kowal, J, Biyani, N, Chami, M, Scherer, S, Rzepiela, AJ, Baumgartner, P et al.. High-Resolution Cryoelectron Microscopy Structure of the Cyclic Nucleotide-Modulated Potassium Channel MloK1 in a Lipid Bilayer. Structure. 2018;26 (1):20-27.e3. doi: 10.1016/j.str.2017.11.012. PubMed PMID:29249605 .
  8. Posson, DJ, Rusinova, R, Andersen, OS, Nimigean, CM. Stopped-Flow Fluorometric Ion Flux Assay for Ligand-Gated Ion Channel Studies. Methods Mol. Biol. 2018;1684 :223-235. doi: 10.1007/978-1-4939-7362-0_17. PubMed PMID:29058195 PubMed Central PMC5971093.
  9. Heer, FT, Posson, DJ, Wojtas-Niziurski, W, Nimigean, CM, Bernèche, S. Mechanism of activation at the selectivity filter of the KcsA K+ channel. Elife. 2017;6 :. doi: 10.7554/eLife.25844. PubMed PMID:28994652 PubMed Central PMC5669632.
  10. Menny, A, Lefebvre, SN, Schmidpeter, PA, Drège, E, Fourati, Z, Delarue, M et al.. Identification of a pre-active conformation of a pentameric channel receptor. Elife. 2017;6 :. doi: 10.7554/eLife.23955. PubMed PMID:28294942 PubMed Central PMC5398890.
  11. Rangl, M, Miyagi, A, Kowal, J, Stahlberg, H, Nimigean, CM, Scheuring, S et al.. Real-time visualization of conformational changes within single MloK1 cyclic nucleotide-modulated channels. Nat Commun. 2016;7 :12789. doi: 10.1038/ncomms12789. PubMed PMID:27647260 PubMed Central PMC5034309.
  12. Kim, DM, Dikiy, I, Upadhyay, V, Posson, DJ, Eliezer, D, Nimigean, CM et al.. Conformational heterogeneity in closed and open states of the KcsA potassium channel in lipid bicelles. J. Gen. Physiol. 2016;148 (2):119-32. doi: 10.1085/jgp.201611602. PubMed PMID:27432996 PubMed Central PMC4969796.
  13. Kim, DM, Nimigean, CM. Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating. Cold Spring Harb Perspect Biol. 2016;8 (5):. doi: 10.1101/cshperspect.a029231. PubMed PMID:27141052 PubMed Central PMC4852806.
  14. Posson, DJ, Rusinova, R, Andersen, OS, Nimigean, CM. Calcium ions open a selectivity filter gate during activation of the MthK potassium channel. Nat Commun. 2015;6 :8342. doi: 10.1038/ncomms9342. PubMed PMID:26395539 PubMed Central PMC4580985.
  15. Rusinova, R, Kim, DM, Nimigean, CM, Andersen, OS. Regulation of ion channel function by the host lipid bilayer examined by a stopped-flow spectrofluorometric assay. Biophys. J. 2014;106 (5):1070-8. doi: 10.1016/j.bpj.2014.01.027. PubMed PMID:24606931 PubMed Central PMC4026792.
  16. McCoy, JG, Rusinova, R, Kim, DM, Kowal, J, Banerjee, S, Jaramillo Cartagena, A et al.. A KcsA/MloK1 chimeric ion channel has lipid-dependent ligand-binding energetics. J. Biol. Chem. 2014;289 (14):9535-46. doi: 10.1074/jbc.M113.543389. PubMed PMID:24515111 PubMed Central PMC3975005.
  17. Kowal, J, Chami, M, Baumgartner, P, Arheit, M, Chiu, PL, Rangl, M et al.. Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1. Nat Commun. 2014;5 :3106. doi: 10.1038/ncomms4106. PubMed PMID:24469021 PubMed Central PMC4086158.
  18. Posson, DJ, Thompson, AN, McCoy, JG, Nimigean, CM. Molecular interactions involved in proton-dependent gating in KcsA potassium channels. J. Gen. Physiol. 2013;142 (6):613-24. doi: 10.1085/jgp.201311057. PubMed PMID:24218397 PubMed Central PMC3840921.
  19. Bhate, MP, Wylie, BJ, Thompson, A, Tian, L, Nimigean, C, McDermott, AE et al.. Preparation of uniformly isotope labeled KcsA for solid state NMR: expression, purification, reconstitution into liposomes and functional assay. Protein Expr. Purif. 2013;91 (2):119-24. doi: 10.1016/j.pep.2013.07.013. PubMed PMID:23916531 PubMed Central PMC3805054.
  20. Posson, DJ, McCoy, JG, Nimigean, CM. The voltage-dependent gate in MthK potassium channels is located at the selectivity filter. Nat. Struct. Mol. Biol. 2013;20 (2):159-66. doi: 10.1038/nsmb.2473. PubMed PMID:23262489 PubMed Central PMC3565016.
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