Where Ideas grow

Structural Biochemistry

ABOUT

We are generally interested on the mechanisms of ion transport across the cell membrane. We have two active research lines, the characterization of the molecular properties of KCNH channels, a family of eukaryotic K+ channels, and the study of the mechanisms that regulate the intracellular concentration of potassium ion in bacteria.

 

RESEARCH

KCNH channels: KCNH channels have important roles in neuronal excitability, cardiac repolarization and cell proliferation. The human ERG (hERG) K+ channel conducts a cardiac repolarizing current and mutations or channel block cause long QT syndrome (LQTS) and catastrophic ventricular arrhythmias. We have developed single-chain antibody fragments (scFv) that bind to the intracellular PAS domain of the hERG channel and modulate its functional properties. These studies suggest that the interactions established by the PAS domain with the rest of the channel are dynamic, changing with the functional states of the channel. Moreover, the scFv molecules increased the amount of current conducted by hERG and shortened the Action Potential Duration in cardiomyocytes, demonstrating therapeutic potential. We are now using these molecules to explore the mechanism of hERG activation.

 

Regulation of intracellular K+ in bacteria: All organisms on Earth accumulate large amounts of K+ inside the cell. In bacteria, intracellular K+ has a role in determining intracellular pressure (turgor), pH and membrane potential. In addition, regulation of intracellular K+ is essential for bacteria to adapt to extracellular changes. Our studies are focused in understanding the molecular properties of K+ transporters that mediate inward and outward ion movement and how these opposing activities are balanced to allow a controlled amount of K+ inside the cell. This fundamental understanding is crucial to define if these transporter systems are potential candidates for anti-microbial strategies.

Cartoon representation of the crystal structure of the MlotiK1 potassium channel with pore domain in grey, S1-S4 domain in red and K+ as magenta spheres. Putative membrane limits are indicated by horizontal lines.