Structure and ion-release mechanism of PIB-4-type ATPases

eLife

Viktoria Bågenholm¹  Gabriela Godaly²  Elena Longhin³  Jonas Eriksson³  Pin Lyu³  Annette Duelli³  Qiaoxia Hu³  Pontus Gourdon³  Christina Grønberg³  Nina Salustros³  Magnus Andersson⁴  Dhani Ram Mahato⁵  Komal Umashankar Rao⁵  Tristan Croll⁵  Gabriele Meloni⁶  Domhnall Iain Henderson⁶  Kaituo Wang⁶ 

[1] Department of Sciences, University of Copenhagen, Copenhagen, Denmark;Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge, United Kingdom;Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Chemistry and Biochemistry, The University of Texas, Dallas, United States;Department of Chemistry, Umeå University, Umeå, Sweden;Department of Laboratory Medicine, Lund University, Lund, Sweden;

关键词: P-type ATPase;    x-ray crystallography;    sulfitobacter sp. NAS14-1;    transition metals;    PIB-4-ATPase;   

DOI  :  10.7554/eLife.73124

来源: DOAJ

【 摘 要 】

Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) 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 PIB-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 PIB-4-ATPase, sCoaT from Sulfitobacter 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 mechanism and diversity of heavy-metal transporters. We reveal several novel P-type ATPase features, including a dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We also establish that the turnover of PIB-ATPases is potassium independent, contrasting to many other P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in for example drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.

【 授权许可】

Unknown