The structure of the Na+,K+-ATPase and mapping of isoform differences and disease-related mutations |
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Authors: | Morth J Preben Poulsen Hanne Toustrup-Jensen Mads S Schack Vivien Rodacker Egebjerg Jan Andersen Jens Peter Vilsen Bente Nissen Poul |
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Institution: | Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, University of Aarhus, Gustav Wieds Vej 10C, Aarhus C, Denmark. |
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Abstract: | The Na+,K+-ATPase transforms the energy of ATP to the maintenance of steep electrochemical gradients for sodium and potassium across the plasma membrane. This activity is tissue specific, in particular due to variations in the expressions of the alpha subunit isoforms one through four. Several mutations in alpha2 and 3 have been identified that link the specific function of the Na+,K+-ATPase to the pathophysiology of neurological diseases such as rapid-onset dystonia parkinsonism and familial hemiplegic migraine type 2. We show a mapping of the isoform differences and the disease-related mutations on the recently determined crystal structure of the pig renal Na+,K+-ATPase and a structural comparison to Ca2+-ATPase. Furthermore, we present new experimental data that address the role of a stretch of three conserved arginines near the C-terminus of the alpha subunit (Arg1003-Arg1005). |
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Keywords: | sodium pump Na+ K+-ATPase ATP1A2 ATP1A3 familial hemiplegic migraine rapid-onset dystonia parkinsonism |
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