title: Structural changes associated with the coupling of ATP hydrolysis and cation transport by the Na pump.
abstract: Most of the residues associated with cation coordination seem to reside within transmembrane segments of the alpha-subunit of the Na,K-ATPase, whereas amino acids which appear to be involved in the coordination of ATP are found in the major cytoplasmic loop between transmembrane segments M4 and M5 (see Lingrel & Kuntzweiler, 1994; Lutsenko & Kaplan, 1995). The coupling of the two functions of cation transport and ATP hydrolysis involved in the active transport of Na and K ions must involve interactions between these two structural units. This paper summarizes recent experimental results and conclusions of studies on the renal Na,K-ATPase which have employed controlled proteolysis in the presence of physiological ligands, chemical modification with a range of reagents and a variety of functional assays. The data provide evidence for movements between specific transmembrane segments associated with cation-binding conformations and coupled changes which take place in the ATP binding domain. The binding of different cations in the cation-binding domain is sensed in the ATP binding domain and manifested as a change in reactivity. This occurs at amino acid residues which are widely spaced in primary structure. It is apparent that structural changes are transmitted through much of the ATP-binding domain as a consequence of the occupancy of the cation-binding domain. We also provide evidence that both the number and identity of cations bound are also sensed in the ATP-binding domain.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA. kaplanj@ohsu.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Kaplan
authors.forename: C
authors.initials: C
authors.lastname: Gatto
authors.forename: J P
authors.initials: JP
authors.lastname: Holden
authors.forename: S J
authors.initials: SJ
authors.lastname: Thornewell
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002412:Cations / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007668:Kidney / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D002412:Cations; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase