TTUHSC School of Medicine
HomeSchool of MedicineCell Physiology and Molecular BiophysicsFacultyLuis G. Cuello

Luis G. Cuello Ph.D

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Cell Physiology and Molecular Biophysics

Center for Membrane Protein Research

Texas Tech University Health Sciences Center

-LABORATORY WEB SITE

Texas Tech University Health Sciences Center
3601 4th Street, STOP 6551
Lubbock, Texas 79430
Office: (806) 743-2525
Lab: (806) 743-2527
FAX: (806) 743-1512
Email: Luis.Cuello@ttuhsc.edu

Research Interests
I have been trained in the use of several biophysical techniques (electrophysiology, spectroscopy and X-ray crystallography) with the aim to understand at the molecular level the intricate relationship between membrane protein structure and function, with special attention to potassium channels. The application of these techniques in tandem have produced the first structural driven kinetic cycle for a potassium channel, which is a crucial technical achievement that would help us to elucidate the molecular basis of channel related diseases and in the "smart" design of new drugs for therapeutic purposes.

The gating cycle of a K+ channel at atomic resolution

Cuello et al. Elife. 2017 Nov 22;6
https://doi.org/10.7554/eLife.28032 @eLife
Figure 6
 
Upper left, Structure of the open and C-type inactivated state at atomic resolution shows a network of water molecules stabilizing KcsA's selectivity filter in the collapsed conformation. Upper right, Inactivating waters behind the selectivity filter are located inside a cavity between to adjacent subunits Inactivation cavity, lower left, Tyrosine 82 in KcsA work as a gatekeeper regulating the flow of water molecules into the inactivation cavity, hence regulating C-type inactivation. Lower right, a small alanine residue at the position 82 allows the free diffusion of water molecules into the inactivation cavity and then accelerating the rate of C-type inactivation.
  • Recent Publications:
  • Tilegenova C, Elberson BW, Cortes DM and Cuello LG. CW-EPR Spectroscopy and Site-Directed Spin Labeling to Study the Structural Dynamics of Ion Channels. Methods Mol. Biol. 2018;1684:279-288

  • Cuello LG, Cortes DM, Perozo E. The gating cycle of a K(+) channel at atomic resolution. Elife 6. pii: e28032, 2017. doi: 10.7554/eLife.28032. PMID: 29165243.

  • Elberson BW, Whisenant TE, Cortes DM, Cuello LG. A cost-effective protocol for the over-expression and purification of fully-functional and more stable Erwinia chrysanthemi ligand-gated ion channel. Protein Expr Purif. 2017 May; 133:177-186

  • Tilegenova C, Cortes DM, Cuello LG. Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel's selectivity filter. Proc. Natl. Acad. Sci. 2017 Mar 21;114(12):3234-3239.

  • Hilgers RH, Kundumani-Sridharan V, Subramani J, Chen LC, Cuello LG, Rusch NJ, Das KC. Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function. Sci. Transl. Med. 2017 Feb 8;9 (376).

  • Selected Publications: (7 out of 33)
  • Tilegenova C, Cortes DM, Cuello LG. Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel's selectivity filter. Proc. Natl. Acad. Sci. 2017 Mar 21;114(12):3234-3239.

  • Krishnan S, Fiori MC, Whisenant T, Cortes MC, Altenberg GA and Cuello LG. An E. coli-Based assay to assess the function of recombinant human hemichannels. SLAS Discov. 2017 Feb; 22(2): 135-143.

  • Elberson BW, Whisenant TE, Cortes DM, Cuello LG. A cost-effective protocol for the over-expression and purification of fully-   functional and more stable Erwinia chrysanthemi ligand-gated ion channel. Protein Expr Purif. 2017 May; 133:177-186.

  • Tilegenova, C, Vemulapally, S, Cortes, DM and Cuello LG. An improved method for the cost-effective expression and purification of large quantities of KcsA. Protein. Expr. Purif. 2016 Nov; 127: 57-60.

  • Zhao R, Dai H, Mendelman N, Cuello LG, Chill JH, Goldstein SA. Designer and natural peptide toxin blockers of the KcsA potassium channel identified by phage display. Proc. Nat. Acad. Sci. USA. Dec 15; 112. 2015.

  • Gonzalez-Gutierrez G, Cuello LG, Nair SK and Grosman C. Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography. Proc. Nat. Acad. Sci. USA110(46):18716-21, 2013.

  • Cuello, L.G.; Jogini, V.; Cortes, D.M. and Perozo, E. Structural mechanism of C-type inactivation in K+ channels. Nature, 2010, Jul 8;466(7303):203-8.

  • Cuello, L.G.; Jogini, V.; Cortes, D.M.; Pan, A.C.; Gagnon, D.G.; Dalmas, O.; Cordero-Morales, J.F.; Chakrapani, S.; Roux, B. and Perozo, E. Structural basis for the coupling between activation and inactivation gates in K+ channels. Nature. 2010, Jul 8;466(7303):272-5.

  • Cordero J, Cuello LG, Zhao Y, Jogini V, Chakrapani S, Roux B and Perozo E. Molecular determinants of gating at the potassium channel selectivity filter. Nature Struct. Mol. Biol. 13(4): 311-8, 2006.

  • Cuello L.G.; Cortes DM, Perozo E. Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer. Science. 2004 Oct 15;306 (5695):491-5.

  • Perozo, E., Cortes, D.M. and Cuello, L.G. Structural Rearrangements Underlying K+ Channel Activation Gating. Science 1999. 285: 73-78.

  • Perozo, E., Cortes, D.M. and Cuello, L.G. Three-dimensional architecture and gating mechanism of a K+ channel studied by EPR spectroscopy. Nature Structure Biology 1998. 5:459-469.

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