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

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Christina Grønberg ◽  
Qiaoxia Hu ◽  
Dhani Ram Mahato ◽  
Elena Longhin ◽  
Nina Salustros ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Metal Binding ◽  
Structural Information ◽  
Release Mechanism ◽  
Ion Release ◽  
Metal Transporters ◽  
Binding Domains ◽  
Cellular Detoxification ◽  
Turn Over ◽  
P Type

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, and provides 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 turn-over 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 e.g. drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.

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

2021 ◽  
Author(s):  
Christina Grønberg ◽  
Qiaoxia Hu ◽  
D Ram Mahato ◽  
Elena Longhin ◽  
Nina Salustros ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Metal Binding ◽  
Structural Information ◽  
Release Mechanism ◽  
Ion Release ◽  
Metal Transporters ◽  
Binding Domains ◽  
Cellular Detoxification ◽  
Turn Over ◽  
P Type

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-ATPases, sCoaT from Sulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy metal binding domains, and provides 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, central histidine. We also establish that the turn-over 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 e.g. drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.

scholarly journals Structural models of the human copper P-type ATPases ATP7A and ATP7B

2012 ◽  
Vol 393 (4) ◽  
pp. 205-216 ◽  
Author(s):  
Pontus Gourdon ◽  
Oleg Sitsel ◽  
Jesper Lykkegaard Karlsen ◽  
Lisbeth Birk Møller ◽  
Poul Nissen
Keyword(s):  
Heavy Metal ◽  
Legionella Pneumophila ◽  
Metal Binding ◽  
Structural Information ◽  
Missense Mutations ◽  
Catalytic Phosphorylation ◽  
The Core ◽  
Binding Domains ◽  
Heavy Metal Binding ◽  
P Type

Abstract The human copper exporters ATP7A and ATP7B contain domains common to all P-type ATPases as well as class-specific features such as six sequential heavy-metal binding domains (HMBD1–HMBD6) and a type-specific constellation of transmembrane helices. Despite the medical significance of ATP7A and ATP7B related to Menkes and Wilson diseases, respectively, structural information has only been available for isolated, soluble domains. Here we present homology models based on the existing structures of soluble domains and the recently determined structure of the homologous LpCopA from the bacterium Legionella pneumophila. The models and sequence analyses show that the domains and residues involved in the catalytic phosphorylation events and copper transfer are highly conserved. In addition, there are only minor differences in the core structures of the two human proteins and the bacterial template, allowing protein-specific properties to be addressed. Furthermore, the mapping of known disease-causing missense mutations indicates that among the heavy-metal binding domains, HMBD5 and HMBD6 are the most crucial for function, thus mimicking the single or dual HMBDs found in most copper-specific P-type ATPases. We propose a structural arrangement of the HMBDs and how they may interact with the core of the proteins to achieve autoinhibition.

scholarly journals Functional analysis of the heavy metal binding domains of the Zn/Cd-transporting ATPase, HMA2, in Arabidopsis thaliana

2008 ◽  
Vol 181 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Chong Kum Edwin Wong ◽  
Renée S. Jarvis ◽  
Sarah M. Sherson ◽  
Christopher S. Cobbett
Keyword(s):  
Heavy Metal ◽  
Functional Analysis ◽  
Arabidopsis Thaliana ◽  
Metal Binding ◽  
Binding Domains ◽  
Heavy Metal Binding

scholarly journals P-Type ATPase Heavy Metal Transporters with Roles in Essential Zinc Homeostasis in Arabidopsis

2004 ◽  
Vol 16 (5) ◽  
pp. 1327-1339 ◽  
Author(s):  
Dawar Hussain ◽  
Michael J. Haydon ◽  
Yuwen Wang ◽  
Edwin Wong ◽  
Sarah M. Sherson ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Zinc Homeostasis ◽  
Metal Transporters ◽  
P Type

Heavy metal binding by mycorrhizal fungi

1994 ◽  
Vol 92 (2) ◽  
pp. 364-368 ◽  
Author(s):  
Ulrich Galli ◽  
Hannes Schuepp ◽  
Christian Brunold
Keyword(s):  
Heavy Metal ◽  
Metal Binding ◽  
Mycorrhizal Fungi ◽  
Heavy Metal Binding

scholarly journals The Role of Aquaporin Overexpression in the Modulation of Transcription of Heavy Metal Transporters under Cadmium Treatment in Poplar

Plants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 54
Author(s):  
Andrea Neri ◽  
Silvia Traversari ◽  
Andrea Andreucci ◽  
Alessandra Francini ◽  
Luca Sebastiani
Keyword(s):  
Heavy Metal ◽  
Transcriptional Response ◽  
Metal Transporters ◽  
Metal Transporter ◽  
Cadmium Treatment ◽  
Tolerance To Cadmium ◽  
Different Response ◽  
Cd Translocation ◽  
Hydroponic Conditions

Populus alba ‘Villafranca’ clone is well-known for its tolerance to cadmium (Cd). To determine the mechanisms of Cd tolerance of this species, wild-type (wt) plants were compared with transgenic plants over-expressing an aquaporin (aqua1, GenBank GQ918138). Plants were maintained in hydroponic conditions with Hoagland’s solution and treated with 10 µM of Cd, renewed every 5 d. The transcription levels of heavy metal transporter genes (PaHMA2, PaNRAMP1.3, PaNRAMP2, PaNRAMP3.1, PaNRAMP3.2, PaABCC9, and PaABCC13) were analyzed at 1, 7, and 60 d of treatment. Cd application did not induce visible toxicity symptoms in wt and aqua1 plants even after 2 months of treatment confirming the high tolerance of this poplar species to Cd. Most of the analyzed genes showed in wt plants a quick response in transcription at 1 d of treatment and an adaptation at 60 d. On the contrary, a lower transcriptional response was observed in aqua1 plants in concomitance with a higher Cd concentration in medial leaves. Moreover, PaHMA2 showed at 1 d an opposite trend within organs since it was up-regulated in root and stem of wt plants and in leaves of aqua1 plants. In summary, aqua1 overexpression in poplar improved Cd translocation suggesting a lower Cd sensitivity of aqua1 plants. This different response might be due to a different transcription of PaNRAMP3 genes that were more transcribed in wt line because of the importance of this gene in Cd compartmentalization.

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