Plastic recognition and electrogenic uniport translocation of 1st-, 2nd-, and 3rd-row transition and post-transition metals by primary-active transmembrane P_1B-2-type ATPase pumps

Authors

• Sameera S. Abeyrathna, The University of Texas at Dallas
• Nisansala S. Abeyrathna, The University of Texas at Dallas
• Priyanka Basak, The University of Texas at Dallas
• Gordon W. Irvine, The University of Texas at Dallas
• LiMei Zhang, University of Nebraska - LincolnFollow
• Gabriele Meloni, The University of Texas at Dallas

Document Type

Article

Date of this Version

2023

Citation

Chem. Sci., 2023, 14, 6059-6078.

DOI: 10.1039/d3sc00347g

Comments

Open access. © 2023 The Author(s). Published by the Royal Society of Chemistry

Abstract

Transmembrane P-type ATPase pumps catalyze the extrusion of transition metal ions across cellular lipid membranes to maintain essential cellular metal homeostasis and detoxify toxic metals. Zn()-pumps of the P-type subclass, in addition to Zn , select diverse metals (Pb, Cdand Hg) at their transmembrane binding site and feature promiscuous metal-dependent ATP hydrolysis in the presence of these metals. Yet, a comprehensive understanding of the transport of these metals, their relative translocation rates, and transport mechanism remain elusive. We developed a platform for the characterization of primary-active Zn()-pumps in proteoliposomes to study metal selectivity, translocation events and transport mechanism in real-time, employing a “multi-probe” approach with fluorescent sensors responsive to diverse stimuli (metals, pH and membrane potential). Together with atomic-resolution investigation of cargo selection by X-ray absorption spectroscopy (XAS), we demonstrate that Zn()-pumps are electrogenic uniporters that preserve the transport mechanism with 1-, 2- and 3-row transition metal substrates. Promiscuous coordination plasticity, guarantees diverse, yet defined, cargo selectivity coupled to their translocation.