Crina Nimigean, Ph.D.

Professor of Physiology and Biophysics

  • Professor of Physiology and Biophysics in Anesthesiology (primary appointment)
  • 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. Sanganna Gari, RR, Montalvo-Acosta, JJ, Heath, GR, Jiang, Y, Gao, X, Nimigean, CM et al.. Correlation of membrane protein conformational and functional dynamics. Nat Commun. 2021;12 (1):4363. doi: 10.1038/s41467-021-24660-1. PubMed PMID:34272395 PubMed Central PMC8285522.
  2. Schmidpeter, PAM, Nimigean, CM. Correlating ion channel structure and function. Methods Enzymol. 2021;652 :3-30. doi: 10.1016/bs.mie.2021.02.016. PubMed PMID:34059287 .
  3. Wague, A, Joseph, TT, Woll, KA, Bu, W, Vaidya, KA, Bhanu, NV et al.. Mechanistic insights into volatile anesthetic modulation of K2P channels. Elife. 2020;9 :. doi: 10.7554/eLife.59839. PubMed PMID:33345771 PubMed Central PMC7781597.
  4. Schmidpeter, PAM, Rheinberger, J, Nimigean, CM. Prolyl isomerization controls activation kinetics of a cyclic nucleotide-gated ion channel. Nat Commun. 2020;11 (1):6401. doi: 10.1038/s41467-020-20104-4. PubMed PMID:33328472 PubMed Central PMC7744796.
  5. Tada, T, Fan, C, Chen, JS, Kaur, R, Stapleford, KA, Gristick, H et al.. An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2. Cell Rep. 2020;33 (12):108528. doi: 10.1016/j.celrep.2020.108528. PubMed PMID:33326798 PubMed Central PMC7705358.
  6. Boiteux, C, Posson, DJ, Allen, TW, Nimigean, CM. Selectivity filter ion binding affinity determines inactivation in a potassium channel. Proc Natl Acad Sci U S A. 2020;117 (47):29968-29978. doi: 10.1073/pnas.2009624117. PubMed PMID:33154158 PubMed Central PMC7703589.
  7. Dandey, VP, Budell, WC, Wei, H, Bobe, D, Maruthi, K, Kopylov, M et al.. Time-resolved cryo-EM using Spotiton. Nat Methods. 2020;17 (9):897-900. doi: 10.1038/s41592-020-0925-6. PubMed PMID:32778833 PubMed Central PMC7799389.
  8. Nimigean, CM. Polyamine block of MthK potassium channels. J Gen Physiol. 2020;152 (7):. doi: 10.1085/jgp.202012614. PubMed PMID:32459330 PubMed Central PMC7335008.
  9. Fan, C, Sukomon, N, Flood, E, Rheinberger, J, Allen, TW, Nimigean, CM et al.. Ball-and-chain inactivation in a calcium-gated potassium channel. Nature. 2020;580 (7802):288-293. doi: 10.1038/s41586-020-2116-0. PubMed PMID:32269335 PubMed Central PMC7153497.
  10. Schmidpeter, PAM, Sukomon, N, Nimigean, CM. Reconstitution of Membrane Proteins into Platforms Suitable for Biophysical and Structural Analyses. Methods Mol Biol. 2020;2127 :191-205. doi: 10.1007/978-1-0716-0373-4_14. PubMed PMID:32112324 .
  11. Tong, A, Petroff, JT 2nd, Hsu, FF, Schmidpeter, PA, Nimigean, CM, Sharp, L et al.. Direct binding of phosphatidylglycerol at specific sites modulates desensitization of a ligand-gated ion channel. Elife. 2019;8 :. doi: 10.7554/eLife.50766. PubMed PMID:31724949 PubMed Central PMC6855808.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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 .
  19. 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.
  20. 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.
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