Transition metal transporting P-type ATPases: terminal metal-binding domains serve as sensors for autoinhibitory tails.

ABSTRACT: Copper is an essential micronutrient and yet is highly toxic to cells at elevated concentrations. P_1B-ATPase proteins are critical for this regulation, providing active extrusion across cellular membranes. One unique molecular adaptation of P_1B-ATPases compared to other P-type ATPases is the presence of metal-binding domains (MBDs) at the cytosolic termini, which however are poorly characterized with an elusive mechanistic role. Here we present the MBD architecture in metal-free and metal-bound forms of the archetype Cu⁺-specific P_1B-ATPase LpCopA, determined using NMR. The MBD is composed of a flexible tail and a structured core with a metal ion binding site defined by three sulfur atoms, one of which is pertinent to the so-called CXXC motif. Fu

SUBMITTER: Hu Q 

PROVIDER: S-EPMC11970713 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature