Luis G. Cuello Laboratory

Center for Membrane Protein Research


Research Interest..
    We are concentrated in elucidating the molecular basis for activation and inactivation gating in ion channels, with especial focus in potassium channels. Currently, we are tackling these problems by pursuing a full structural and functional characterization of KcsA trapped in different kinetic states by using functional, spectroscopic and crystallography approaches. The finding of a new KcsA mutant that “freeze” the channel in the open conformation will allow us to determine the contribution of the activation gate, the ion cavity and the selectivity filter in the normal functioning of a potassium channel pore domain, from a functional and structural point of view.
    We also are pursuing a complete structural and functional characterization of the gating process in the bacteria inward rectifier K+ channel, Kirbac 1.1, this is actively pursued in our laboratory with the intention to shed light on the functioning of these interesting but unknown members of the potassium channel family.
    By having a better understanding of the gating-related conformational changes in a potassium channel, we will provide a structural framework to understand the molecular basis of drug-induced arrhythmias and how some drugs selectively target the inactivated state of the Herg potassium channel. The elucidation the molecular basis of Herg blockade and drug-induced arrhythmia will assist us in the design of safer and novel therapeutic drugs.

X-ray structures of KcsA in the closed state (Zhou et al. 2001) left panel and open-inactivated right panel (Cuello et al. unpublished data)