Luis G. Cuello, Ph.D.
Professor of Cell Physiology & Molecular Biophysics
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 Interest:
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
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.
New Federal Funding |
|
| NIH RO1 (High-resolution crystallographic and functional studies of K+ channel gating ) | 2018-2022 |
| Welch Foundation (Crystallographic and functional studies on the novel role of water molecules in K+
channel C-type inactivation gating) |
2018-2021 |
Selected Publications:
| Lewis A, McCrossan ZA, Manville RW, Popa MO, Cuello LG, Goldstein SAN. TOK channels use the two gates in classical K+ channels to achieve outward rectification [published online ahead of print, 2020 Jun 10]. FASEB J. 2020;10.1096/fj.202000545R. doi:10.1096/fj.202000545R | |
| Coonen L, Mayeur E, De Neuter N, Snyders DJ, Cuello LG, Labro AJ. The Selectivity Filter Is Involved in the U-Type Inactivation Process of Kv2.1 and Kv3.1 Channels. Biophys J. 2020;118(10):2612鈥�2620. doi:10.1016/j.bpj.2020.03.032 | |
| H茅nault CM, Govaerts C, Spurny R, Brams M, Estrada A, Lynch J, Bertrand D, Pardon E, Evans G, Woods K, Elberson BW, Cuello LG, Brannigan G, Nury H, Steyaert JE, Baenziger JE and Ulens C (2019). A lipid recognition site at a transmembrane helix kink shapes the agonist response of a pentameric ligand-gated ion channel. Under revision in Nature Chemical Biology. (2019) Oct 7. doi: 10.1038/s41589-019-0369-4. [Epub ahead of print]. | |
| Tilegenova C, Cortes DM, Jahovic N, Hardy E, Hariharan P, Guan L and Cuello LG (2019). Structure, function and ion binding properties of a K+ channel stabilized in the 2,4-ion bound configuration. Under revision in Proc. Natl. Acad. Sci. 2019. | |
| Li J, Ostmeyer J, Cuello LG, Perozo E and Roux B (2018). Rapid constriction of the selectivity filter underlies C-type inactivation in the KcsA potassium channel. J Gen. Physiology. 2018 Oct 1; 150 (10): 1408-1420. Commented by Delemonte L. J. Gen Physiology. Oct 1; 150 (10): 1356. | |
| Labron AJ, Cortes DM, Tilegenova C and Cuello LG (2018). Inverted allosteric coupling between activation and inactivation gates n K+ channels. PNAS. May 22; 115, 5426-5431. | |
| Tilegenova C, Elberson BW, Marien Cortes D, Cuello LG (2018). CW-EPR Spectroscopy and Site-Directed Spin Labeling to Study the Structural Dynamics of Ion Channels. | |
| Cuello LG, D Marien Cortes, Eduardo Perozo (2017). The gating cycle of a K+ channel at atomic resolution | |
| Elberson BW, Whisenant TE, Cortes DM, Cuello LG (2017). A cost-effective protocol for the over-expression and purification of fully-functional and more stable Erwinia chrysanthemi ligand-gated ion channel. | |
| Cholpon Tilegenova, D. Marien Cortes, Luis G. Cuello (2017). Hysteresis of KcsA potassium channel's activation鈥� deactivation gating is caused by structural changes at the channel鈥檚 selectivity filter. | |
| Hilgers RH, Kundumani-Sridharan V, Subramani J, Chen LC, Cuello LG, Rusch NJ, Das KC (2017). Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function. | |
| Cholpon Tilegenova, D. Marien Cortes and Luis G. Cuello (2017). Hysteresis of KcsA potassium channel's activation鈥� deactivation gating is caused by structural changes at the channel鈥檚 selectivity filter. | |
| Krishnan S, Fiori MC, Whisenant TE, Cortes DM, Altenberg GA, Cuello LG (2017). An Escherichia coli-Based Assay to Assess the Function of Recombinant Human Hemichannels. | |
| Elberson BW, Whisenant TE, Cortes DM, Cuello LG (2017). A cost-effective protocol for the over-expression and purification of fully-functional and more stable Erwinia chrysanthemi ligand-gated ion channel. | |
| Tilegenova C, Vemulapally S, Cortes DM, Cuello LG (2016). An improved method for cost-effective expression and purification of large quantities of KcsA. | |
| Zhao R, Dai H, Mendelman N, Cuello LG, Chill JH, Goldstein SA (2015). Designer and natural peptide toxin blockers of the KcsA potassium channel identified by phage display. | |
| Gonzalez-Gutierrez G, Cuello LG, Nair SK, Grosman C (2013). Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography. | |
| Luis G. Cuello, Vishwanath Jogini, D. Marien Cortes, Eduardo Perozo (2010). Structural mechanism of C-type inactivation in K+ channels. | |
| Cuello LG, Jogini V, Cortes DM, Pan AC, Gagnon DG, Dalmas O, Cordero-Morales JF, Chakrapani S, Roux B, Perozo E (2010). Structural basis for the coupling between activation and inactivation gates in K(+) channels. | |
| Cordero-Morales JF, Cuello LG, Zhao Y, Jogini V, Cortes DM, Roux B, Perozo E (2006). Molecular determinants of gating at the potassium-channel selectivity filter. | |
| Cuello LG, Cortes DM, Perozo E (2004). Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer. | |
| Perozo E, Cortes DM, Cuello LG (1999). Structural rearrangements underlying K+-channel activation gating. | |
| Eduardo Perozo, D. Marien Cortes & Luis G. Cuello (1998). Three-dimensional architecture and gating mechanism of a K+ channel studied by EPR spectroscopy. |
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