1. Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland

Correspondence to: Kaspar P. Locher¹ Correspondence and requests for materials should be addressed to K.P.L. (Email: kaspar.locher@mol.biol.ethz.ch).

Abstract

ATP-binding cassette (ABC) transporter proteins carry diverse substrates across cell membranes¹. Whereas clinically relevant ABC exporters are implicated in various diseases or cause multidrug resistance of cancer cells^{2, 3}, bacterial ABC importers are essential for the uptake of nutrients⁴, including rare elements such as molybdenum. A detailed understanding of their mechanisms requires direct visualization at high resolution and in distinct conformations. Our recent structure of the multidrug ABC exporter Sav1866 has revealed an outward-facing conformation of the transmembrane domains coupled to a closed conformation of the nucleotide-binding domains, reflecting the ATP-bound state⁵. Here we present the 3.1 Å crystal structure of a putative molybdate transporter (ModB₂C₂) from Archaeoglobus fulgidus in complex with its binding protein (ModA). Twelve transmembrane helices of the ModB subunits provide an inward-facing conformation, with a closed gate near the external membrane boundary. The ATP-hydrolysing ModC subunits reveal a nucleotide-free, open conformation, whereas the attached binding protein aligns the substrate-binding cleft with the entrance to the presumed translocation pathway. Structural comparison of ModB₂C₂A with Sav1866 suggests a common alternating access and release mechanism, with binding of ATP promoting an outward-facing conformation and dissociation of the hydrolysis products promoting an inward-facing conformation.

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