Structure and mechanism of Na,K-ATPase:: Functional sites and their interactions

被引:427
作者
Jorgensen, PL
Håkansson, KO
Karlish, SJD
机构
[1] Univ Copenhagen, August Krogh Inst, Biomembrane Ctr, DK-2100 Copenhagen OE, Denmark
[2] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel
关键词
Na-K-pump homology models; ATP binding; Na+ and K+ ion binding; energy transduction mechanism;
D O I
10.1146/annurev.physiol.65.092101.142558
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The cell membrane Na,K-ATPase is a member of the P-type family of active cation transport proteins. Recently the molecular structure of the related sarcoplasmic reticulum Ca-ATPase in an E-1 conformation has been determined at 2.6 Angstrom resolution. Furthermore, theoretical models of the Ca-ATPase in E-2 conformations are available. As a result of these developments, these structural data have allowed construction of homology models that address the central questions of mechanism of active cation transport by all P-type cation pumps. This review relates recent evidence on functional sites of Na,K-ATPase for the substrate (ATP), the essential cofactor (Mg2+ ions), and the transported cations (Na+ and K+) to the molecular structure. The essential elements of the Ca-ATPase structure, including 10 transmembrane helices and well-defined N, P, and A cytoplasmic domains, are common to all P-II-type pumps such as Na,K-ATPase and H,K-ATPases. However, for Na,K-ATPase and H,K-ATPase, which consist of both alpha- and beta-subunits, there may be some detailed differences in regions of subunit interactions. Mutagenesis, proteolytic cleavage, and transition metal-catalyzed oxidative cleavages are providing much evidence about residues involved in binding of Na+, K+, ATP, and Mg2+ ions and changes accompanying E-1-E-2 or E-1-P-E-2-P conformational transitions. We discuss this evidence in relation to N, P, and A cytoplasmic domain interactions, and long-range interactions between the active site and the Na+ and K+ sites in the transmembrane segments, for the different steps of the catalytic cycle.
引用
收藏
页码:817 / 849
页数:37
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