P1 B -ATPases are among the most common resistance factors to metal-induced stress. Belonging to the superfamily of P-type ATPases， they are capable of exporting transition metal ions at the expense of adenosine triphosphate (ATP) hydrolysis. P1 B -ATPases share a conserved structure of three cytoplasmic domains linked by a transmembrane domain. In addition， they possess a unique class of domains located at the N-terminus. In bacteria， these domains are primarily associated with metal binding and either occur individually or as serial copies of each other. Within this study， the roles of the two adjacent metal-binding domains (MBDs) of CopA， the copper export ATPase of Escherichia coli were investigat... More
P1 B -ATPases are among the most common resistance factors to metal-induced stress. Belonging to the superfamily of P-type ATPases， they are capable of exporting transition metal ions at the expense of adenosine triphosphate (ATP) hydrolysis. P1 B -ATPases share a conserved structure of three cytoplasmic domains linked by a transmembrane domain. In addition， they possess a unique class of domains located at the N-terminus. In bacteria， these domains are primarily associated with metal binding and either occur individually or as serial copies of each other. Within this study， the roles of the two adjacent metal-binding domains (MBDs) of CopA， the copper export ATPase of Escherichia coli were investigated. From biochemical and physiological data， we deciphered the protein-internal pathway of copper and demonstrate the distal N-terminal MBD to possess a function analogous to the metallochaperones of related prokaryotic copper resistance systems， that is its involvement in the copper transfer to the membrane-integral ion-binding sites of CopA. In contrast， the proximal domain MBD2 has a regulatory role by suppressing the catalytic activity of CopA in absence of copper. Furthermore， we propose a general functional divergence of tandem MBDs in P1 B -ATPases， which is governed by the length of the inter-domain linker.
