Structure-function relationship in P-type ATPases—a biophysical approach

Abstract

P-type ATPases are a large family of membrane proteins that perform active ion transport across biological membranes. In these proteins the energy-providing ATP hydrolysis is coupled to ion-transport that builds up or maintains the electrochemical potential gradients of one or two ion species across the membrane. P-type ATPases are found in virtually all eukaryotic cells and also in bacteria, and they are transporters of a broad variety of ions. So far, a crystal structure with atomic resolution is available only for one species, the SR Ca-ATPase. However, biochemical and biophysical studies provide an abundance of details on the function of this class of ion pumps. The aim of this review is to summarize the results of preferentially biophysical investigations of the three best-studied ion pumps, the Na,K-ATPase, the gastric H,K-ATPase, and the SR Ca-ATPase, and to compare functional properties to recent structural insights with the aim of contributing to the understanding of their structure-function relationship.

Electrogenic transport of sodium ions in cytoplasmic and extracellular ion access channels of Na+,K+-ATPase probed by admittance measurement technique

“…The location of the third sodium binding site, which is unique for the Na + ,K + -ATPase, is not clear so far. The responsible amino acids are proposed either by molecular modeling or by studying the effect of amino-acid substitution on transport function [6][7][8][9][10].…”

“…Essential information on the access channels of the Na + ,K + -ATPase was obtained from the studies of electrogenic ion transport performed with the aid of electro- [6,[11][12][13]. These experiments allow the evaluation the dielectric coefficients of distinct electrogenic transport steps.…”

“…These coefficients characterize the relative depths of charge movements inside the protein. It has been demonstrated by various experimental techniques that the major contribution to the electric current through the membrane is the ion movement associated with the third Na + released (as first ion) through the extracellular access channel [6,12,[14][15][16]. The large value of the dielectric coefficient of this process was explained by the assumption that the extracellular access channel for the third sodium ion is deep and narrow and its binding site is placed closer to the cytoplasmic side of the protein [8].…”

Photodynamic Inactivation of the Na,K-ATPase Occurs via Different Pathways

“…In brief, substrate-induced transitions (i.e., the partial reactions) that move electric charge in and out of the membrane domain of the transport protein cause changes of the fluorescence intensity of the dye (Pedersen et al, 2001). This method was repeatedly used in order to gain insight into the transport kinetics of the Na,KATPase (Heyse et al, 1994, Apell, 2003 and of the SR Ca-ATPase (Peinelt & Apell, 2002), and to study the effects of free radicals of water radiolysis on the Na,K-ATPase (Mense et al, 1997).…”

Παράγοντες Που Επηρεάζουν Την Απελευθέρωση Του Μονοξειδίου Του Αζώτου (NO) Στους Αεραγωγούς

“…Στις ΛΜΙ υπάρχει η ασβεστιοΑΤΡάση του σαρκοπλασματικού/ενδοπλασματικού δικτύου (SERCA2b χρησιμοποιώντας ενέργεια από την υδρόλυση του ΑΤΡ [66] . Είναι η κυριότερη από τις ισομορφές του ενζύμου SERCA.…”