Work

Arginine substitution of a cysteine in transmembrane helix M8 converts Na + ,K + -ATPase to an electroneutral pump similar to H + ,K + -ATPase

Year: 2016

Type: article

Abstract: Significance This study explores the structural basis for the difference between the closely related Na + ,K + -ATPase and H + ,K + -ATPase with respect to ion transport stoichiometry, electrogenicity, and cation selectivity, which has long been an enigma. A cysteine in the membrane domain of Na + ,K + -ATPase is substituted by arginine in H + ,K + -ATPase and has been found to be replaced by phenylalanine in a patient with alternating hemiplegia of childhood. These substitutions affect the functioning of the Na + -specific site of Na + ,K + -ATPase profoundly. The positively charged side chain of the arginine present in H + ,K + -ATPase serves as an internal cation that replaces bound Na + , thus explaining how H + ,K + -ATPase avoids binding and transporting Na + at this site, thereby performing electroneutral transport, despite the general structural and functional resemblance to the electrogenic Na + ,K + -ATPase.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1617951114

Authors: Rikke Holm, Jaanki Khandelwal, Anja P. Einholm, Jens P. Andersen, Pablo Artigas, Bente Vilsen

Institutions: Aarhus University, Texas Tech University, Texas Tech University Health Sciences Center

Language: English

Topic: ATP Synthase and ATPases Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green