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. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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 .
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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 .
  13. 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.
  14. 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.
  15. Verdon, G, Boudker, O. Crystal structure of an asymmetric trimer of a bacterial glutamate transporter homolog. Nat. Struct. Mol. Biol. 2012;19 (3):355-7. doi: 10.1038/nsmb.2233. PubMed PMID:22343718 PubMed Central PMC3633560.
  16. Boudker, O, Verdon, G. Structural perspectives on secondary active transporters. Trends Pharmacol. Sci. 2010;31 (9):418-26. doi: 10.1016/j.tips.2010.06.004. PubMed PMID:20655602 PubMed Central PMC2933288.
  17. Reyes, N, Ginter, C, Boudker, O. Transport mechanism of a bacterial homologue of glutamate transporters. Nature. 2009;462 (7275):880-5. doi: 10.1038/nature08616. PubMed PMID:19924125 PubMed Central PMC2934767.
  18. Boudker, O, Ryan, RM, Yernool, D, Shimamoto, K, Gouaux, E. Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter. Nature. 2007;445 (7126):387-93. doi: 10.1038/nature05455. PubMed PMID:17230192 .
  19. Yernool, D, Boudker, O, Jin, Y, Gouaux, E. Structure of a glutamate transporter homologue from Pyrococcus horikoshii. Nature. 2004;431 (7010):811-8. doi: 10.1038/nature03018. PubMed PMID:15483603 .
  20. Yernool, D, Boudker, O, Folta-Stogniew, E, Gouaux, E. Trimeric subunit stoichiometry of the glutamate transporters from Bacillus caldotenax and Bacillus stearothermophilus. Biochemistry. 2003;42 (44):12981-8. doi: 10.1021/bi030161q. PubMed PMID:14596613 .
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