biostudies-literatureGronberg CCarlsbergfondetChina Scholarship CouncilNational Supercomputer CentreKnut och Alice Wallenbergs StiftelseSwedish Research CouncilThe memorial foundation of manufacturer Vilhelm Pedersen and wife - and the Aarhus Wilson consortiumLundbeck FoundationNational Institute of General Medical SciencesCrafoordska StiftelsenThe Independent Research Fund DenmarkCarl Tryggers Stiftelse för Vetenskaplig ForskningBrødrene HartmannPer-Eric and Ulla SchybergRobert A Welch FoundationAgnes og Poul Friis FondLundbeckfondenNovo Nordisk FondenAugustinus FondenWellcome TrustNIGMS NIH HHSNational Science FoundationSwedish Heart-Lung Foundatione73124https://www.ebi.ac.uk/biostudies/studies/S-EPMC8880997biostudies-literatureUnknown10Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (P_IB) ATPases are crucial for homeostasis, conferring cellular detoxification and redistribution through transport of these ions across cellular membranes. No structural information is available for the P_IB-4-ATPases, the subclass with the broadest cargo scope, and hence even their topology remains elusive. Here, we present structures and complementary functional analyses of an archetypal P_IB-4-ATPase, sCoaT from <i>Sulfitobacter</i> sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy-metal-binding domains (HMBDs), and provide fundamentally new insights into the mechanismeLifeStructure and ion-release mechanism of P&lt;sub&gt;IB-4&lt;/sub&gt;-type ATPases.PMC888099738267CF15-0542R35GM128704AT-2073-202103272013_01_06419039-00273AR35 GM128704A2951920200378R324-2019-1855CHE-2045984R133-A126892020-03840R35GM128704)2020.01942015.0131AT-1935-2017032516-1992201806522021/5-362209407/Z/17/ZCTS 17:22R313-2019-774NNF13OC000747120170818218-2016-1548R263-2017-4406R139-2012-12689CHE- 2045984R218-2016-15482016-04474NNF18SA0034956Gronberg CCroll TGodaly GMahato DRAndersson MWang KDuelli ABagenholm VMeloni GSalustros NHenderson DILonghin EEriksson JGourdon PHu QRao KULyu PfalseStructure and ion-release mechanism of P&lt;sub&gt;IB-4&lt;/sub&gt;-type ATPases.Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (P_IB) ATPases are crucial for homeostasis, conferring cellular detoxification and redistribution through transport of these ions across cellular membranes. No structural information is available for the P_IB-4-ATPases, the subclass with the broadest cargo scope, and hence even their topology remains elusive. Here, we present structures and complementary functional analyses of an archetypal P_IB-4-ATPase, sCoaT from <i>Sulfitobacter</i> sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy-metal-binding domains (HMBDs), and provide fundamentally new insights into the mechanism2021-01-01T00:00:00Z2021 Dec2026-05-30T15:13:47.924Z2025-04-19T22:36:10.173ZS-EPMC88809973495159010.7554/eLife.73124