Copper-dependent ATP7B N-terminal domain dynamics in two reaction-cycle intermediates

Abstract

Membrane proteins control the flow of ions across biological membranes by selective import or export and are of vital importance for all living cells. Disturbances in ion transport can cause severe diseases such as Wilson’s disease, which is caused by mutations in the human copper-transporting P-type ATPase ATP7B. ATP7B activity is regulated by a dynamic N-terminal domain consisting of six metal binding domains (MBDs) that move as rigid bodies and interact transiently with each other and the core transporter in a copper-dependent manner.