Associate Professor of Cell Physiology & Molecular Biophysics

luis cuello
 

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

gating cycle

 

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:

  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.
ncbi 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.  
 ncbi Cuello LG, D Marien Cortes, Eduardo Perozo (2017). The gating cycle of a K+ channel at atomic resolution
 ncbi 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.
 ncbi Cholpon Tilegenova, D. Marien Cortes, Luis G. Cuello (2017). Hysteresis of KcsA potassium channel's activation– deactivation gating is caused by structural changes at the channel’s selectivity filter.
 ncbi 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.
 ncbi Cholpon Tilegenova, D. Marien Cortes and Luis G. Cuello (2017). Hysteresis of KcsA potassium channel's activation– deactivation gating is caused by structural changes at the channel’s selectivity filter.
 ncbi 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.
ncbi  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.
 ncbi Tilegenova C, Vemulapally S, Cortes DM, Cuello LG (2016).  An improved method for cost-effective expression and purification of large quantities of KcsA.
 ncbi 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.
ncbi 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.
ncbi Luis G. Cuello, Vishwanath Jogini, D. Marien Cortes, Eduardo Perozo (2010). Structural mechanism of C-type inactivation in K+ channels. 
ncbi 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.
ncbi 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.
ncbi Cuello LG, Cortes DM, Perozo E (2004). Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer.
ncbi Perozo E, Cortes DM, Cuello LG (1999). Structural rearrangements underlying K+-channel activation gating.
ncbi 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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Luis Cuello, Ph.D.

(806) 743-2525

luis.cuello@ttuhsc.edu