Structure and ion-release mechanism of P IB-4-type ATPases

Christina Grønberg, Qiaoxia Hu, Dhani Ram Mahato, Elena Longhin, Nina Salustros, Annette Duelli, Pin Lyu, Viktoria Bågenholm, Jonas Eriksson, Komal Umashankar Rao, Domhnall Iain Henderson, Gabriele Meloni, Magnus Andersson, Tristan Croll, Gabriela Godaly, Kaituo Wang, Pontus Gourdon

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


Abstract 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.
ArtikelnummerPMID: 34951590
Antal sidor21
StatusPublished - 2022

Ämnesklassifikation (UKÄ)

  • Biokemi och molekylärbiologi
  • Biofysik


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