Olga Boudker, Ph.D.

Professor of Physiology and Biophysics

Howard Hughes Medical Institute Investigator


212-746-6634

Whitney Pavillion
525 East 68th Street, Room W-207
New York, NY 10065


Techniques

Research Areas


Research Summary:

Lipid membranes define living cells, separating the internal cellular processes from the external environment. Our lab focuses on how the cells interact with the environment, especially how they move materials across the membranes. Specialized integral membrane proteins, called transporters, accomplish the task. They work as miniature machines that use the energy of ATP or trans-membrane gradients of ions to pump nutrients, neurotransmitters, waste and drugs in or out of the cells. We aim to define the molecular motions that underlie their activity. Furthermore, we decipher the structural features that define the rate at which these machines work and how they are regulated in the cells and through the use of pharmacological tools. Finally, we are interested in the evolution of transporters. Specifically, in how they have adapted to the changes of cellular environments and diversified their functional capabilities. To answer these questions we use a combination of techniques. We use crystallography and Cryo-EM to define the high-resolution structures of key functional states of transporters; single molecule FRET TIRF microscopy and NMR to probe their dynamics; biochemical approaches and isothermal titration calorimetry to probe their function and energetics; and bioinformatics to follow evolution.

Recent Publications:

  1. Qiu, B, Matthies, D, Fortea, E, Yu, Z, Boudker, O. Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport. Sci Adv. 2021;7 (10):. doi: 10.1126/sciadv.abf5814. PubMed PMID:33658209 PubMed Central PMC7929514.
  2. Huysmans, GHM, Ciftci, D, Wang, X, Blanchard, SC, Boudker, O. The high-energy transition state of the glutamate transporter homologue GltPh. EMBO J. 2021;40 (1):e105415. doi: 10.15252/embj.2020105415. PubMed PMID:33185289 PubMed Central PMC7780239.
  3. Wang, X, Boudker, O. Large domain movements through the lipid bilayer mediate substrate release and inhibition of glutamate transporters. Elife. 2020;9 :. doi: 10.7554/eLife.58417. PubMed PMID:33155546 PubMed Central PMC7682989.
  4. Matin, TR, Heath, GR, Huysmans, GHM, Boudker, O, Scheuring, S. Millisecond dynamics of an unlabeled amino acid transporter. Nat Commun. 2020;11 (1):5016. doi: 10.1038/s41467-020-18811-z. PubMed PMID:33024106 PubMed Central PMC7538599.
  5. Ciftci, D, Huysmans, GHM, Wang, X, He, C, Terry, D, Zhou, Z et al.. Single-molecule transport kinetics of a glutamate transporter homolog shows static disorder. Sci Adv. 2020;6 (22):eaaz1949. doi: 10.1126/sciadv.aaz1949. PubMed PMID:32523985 PubMed Central PMC7259943.
  6. Huang, Y, Wang, X, Lv, G, Razavi, AM, Huysmans, GHM, Weinstein, H et al.. Use of paramagnetic 19F NMR to monitor domain movement in a glutamate transporter homolog. Nat Chem Biol. 2020;16 (9):1006-1012. doi: 10.1038/s41589-020-0561-6. PubMed PMID:32514183 PubMed Central PMC7442671.
  7. Oh, S, Boudker, O. Kinetic mechanism of coupled binding in sodium-aspartate symporter GltPh. Elife. 2018;7 :. doi: 10.7554/eLife.37291. PubMed PMID:30255846 PubMed Central PMC6175574.
  8. Riederer, EA, Focke, PJ, Georgieva, ER, Akyuz, N, Matulef, K, Borbat, PP et al.. A facile approach for the in vitro assembly of multimeric membrane transport proteins. Elife. 2018;7 :. doi: 10.7554/eLife.36478. PubMed PMID:29889023 PubMed Central PMC6025958.
  9. Jentsch, JA, Kiburu, I, Pandey, K, Timme, M, Ramlall, T, Levkau, B et al.. Structural basis of sterol binding and transport by a yeast StARkin domain. J Biol Chem. 2018;293 (15):5522-5531. doi: 10.1074/jbc.RA118.001881. PubMed PMID:29463678 PubMed Central PMC5900764.
  10. Scopelliti, AJ, Font, J, Vandenberg, RJ, Boudker, O, Ryan, RM. Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5. Nat Commun. 2018;9 (1):38. doi: 10.1038/s41467-017-02444-w. PubMed PMID:29295993 PubMed Central PMC5750217.
  11. Ruan, Y, Miyagi, A, Wang, X, Chami, M, Boudker, O, Scheuring, S et al.. Direct visualization of glutamate transporter elevator mechanism by high-speed AFM. Proc Natl Acad Sci U S A. 2017;114 (7):1584-1588. doi: 10.1073/pnas.1616413114. PubMed PMID:28137870 PubMed Central PMC5320997.
  12. Drew, D, Boudker, O. Shared Molecular Mechanisms of Membrane Transporters. Annu Rev Biochem. 2016;85 :543-72. doi: 10.1146/annurev-biochem-060815-014520. PubMed PMID:27023848 .
  13. Aseervatham, J, Tran, L, Machaca, K, Boudker, O. The Role of Flexible Loops in Folding, Trafficking and Activity of Equilibrative Nucleoside Transporters. PLoS One. 2015;10 (9):e0136779. doi: 10.1371/journal.pone.0136779. PubMed PMID:26406980 PubMed Central PMC4583308.
  14. Boudker, O, Oh, S. Isothermal titration calorimetry of ion-coupled membrane transporters. Methods. 2015;76 :171-182. doi: 10.1016/j.ymeth.2015.01.012. PubMed PMID:25676707 PubMed Central PMC4912014.
  15. Akyuz, N, Georgieva, ER, Zhou, Z, Stolzenberg, S, Cuendet, MA, Khelashvili, G et al.. Transport domain unlocking sets the uptake rate of an aspartate transporter. Nature. 2015;518 (7537):68-73. doi: 10.1038/nature14158. PubMed PMID:25652997 PubMed Central PMC4351760.
  16. Verdon, G, Oh, S, Serio, RN, Boudker, O. Coupled ion binding and structural transitions along the transport cycle of glutamate transporters. Elife. 2014;3 :e02283. doi: 10.7554/eLife.02283. PubMed PMID:24842876 PubMed Central PMC4051121.
  17. Akyuz, N, Altman, RB, Blanchard, SC, Boudker, O. Transport dynamics in a glutamate transporter homologue. Nature. 2013;502 (7469):114-8. doi: 10.1038/nature12265. PubMed PMID:23792560 PubMed Central PMC3829612.
  18. Ginter, C, Kiburu, I, Boudker, O. Chemical catalysis by the translocator protein (18 kDa). Biochemistry. 2013;52 (21):3609-11. doi: 10.1021/bi400364z. PubMed PMID:23651039 .
  19. Reyes, N, Oh, S, Boudker, O. Binding thermodynamics of a glutamate transporter homolog. Nat Struct Mol Biol. 2013;20 (5):634-40. doi: 10.1038/nsmb.2548. PubMed PMID:23563139 PubMed Central PMC3711778.
  20. Georgieva, ER, Borbat, PP, Ginter, C, Freed, JH, Boudker, O. Conformational ensemble of the sodium-coupled aspartate transporter. Nat Struct Mol Biol. 2013;20 (2):215-21. doi: 10.1038/nsmb.2494. PubMed PMID:23334289 PubMed Central PMC3565060.
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