Abstract
In the P-domain, the 369-DKTGTLT and the 709-GDGVNDSPALKK segment are highly conserved during evolution of P-type E1–E2-ATPase pumps irrespective of their cation specificities. The focus of this article is on evaluation of the role of the amino acid residues in the P domain of the α subunit of Na,K-ATPase for the E1P[3Na]→ E2P[2Na] conversion, the K+-activated dephosphorylation, and the transmission of these changes to and from the cation binding sites. Mutations of residues in the TGDGVND loop show that Asp710 is essential, and Asn713 is important, for Mg2+ binding and formation of the high-energy MgE1P[3Na] intermediate. In contrast Asp710 and Asp713 do not contribute to Mg2+ binding in the E2P–ouabain complex. Transition to E2P thus involves a shift of Mg2+ coordination away from Asp710 and Asn713 and the two residues become more important for K+-activated hydrolysis of the acyl phosphate bond at Asp369. Transmission of structural changes between the P-domain and cation sites in the membrane domain is evaluated in light of the protein structure, and the information from proteolytic or metal-catalyzed cleavage and mutagenesis studies.
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Jorgensen, P.L., Jorgensen, J.R. & Pedersen, P.A. Role of Conserved TGDGVND-Loop in Mg2+ Binding, Phosphorylation, and Energy Transfer in Na,K-ATPase. J Bioenerg Biomembr 33, 367–377 (2001). https://doi.org/10.1023/A:1010611322024
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DOI: https://doi.org/10.1023/A:1010611322024