A novel mechanism of P-type ATPase autoinhibition involving both termini of the protein

Abstract

The activity of many P-type ATPases is found to be regulated by interacting proteins or autoinhibitory elements located in Nor C-terminal extensions.Anextended C terminus of fungal and plant P-type plasma membrane H+-ATPases has long been recognized to be part of a regulatory apparatus involving an autoinhibitory domain. Here we demonstrate that both theNand the C termini of the plant plasma membrane H+-ATPase are directly involved in controlling the pump activity state and that N-terminal displacements are coupled to secondary modifications taking place at the C-terminal end. This identifies the first group of P-type ATPases for which both ends of the polypeptide chain constitute regulatory domains, which together contribute to the autoinhibitory apparatus. This suggests an intricate mechanism of cis-regulation with both termini of the protein communicating to obtain the necessary control of the enzyme activity state. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.