Challenging the H,K-ATPase: Can you imagine a salty gastric juice?

WANDA M. VALSECCHI; ROLANDO C. ROSSI; NICOLE T. CERF; JOAQUIN N. MONTERO ESTEVES; SANTIAGO E. FARAJ; MÓNICA R. MONTES

Buenos Aires

Congreso; Biofísica en tiempos de COVID-19 - Primeras Jornadas Virtuales de la Sociedad Argentina de Biofísica.; 2020

Sociedad Argentina de Biofísica

The P-type ATPase family (P-ATPases) is responsible for carrying out essential functions such as the maintenance of electrochemical gradients, asymmetric distribution of lipids in the membranes and extrusion of toxic heavy metals in all life forms. For this reason, they are related to the development of certain pathological conditions and have become important therapeutic targets1. Thus, the study of their mechanism of transport and structure results of great interest. The gastric H,K-ATPase is a membrane protein located in the parietal cells of the stomach, which allows the formation of an acidic medium with a pH close to 1 in the gastric lumen. H,K-ATPase carries out the ATP-dependent exchange of intracellular protons for extracellular potassium ions. Since the gastric H,K-ATPase is responsible for the final step of acid secretion, this enzyme is the main therapeutic target in the treatment of acid peptic disorders2.Although H,K-ATPase has been studied for several years, the stoichiometry and the molecular mechanism of proton transport are still under discussion.To shed light on the specificity of cation binding, and given the great similarity between kidney Na,K-ATPase and gastric H,K-ATPase, we analyzed if Na+ is a congener of H+ regarding conformational changes, cation occlusion, and ATPase activity in the H,K-ATPase. We discuss the proton transport system in terms of the interaction between ion binding residues and protons or hydronium ions.