8Q75

Copper-transporting ATPase HMA4 in E2P state with AlF

Summary for 8Q75

• Entry DOI: 10.2210/pdb8q75/pdb
• EMDB information: 18204
• Descriptor: Copper-transporting ATPase HMA4, TETRAFLUOROALUMINATE ION, MAGNESIUM ION (3 entities in total)
• Functional Keywords: p-atpase, transport protein
• Biological source: Oryza sativa Japonica Group (Japanese rice)
• Total number of polymer chains: 1
• Total formula weight: 94871.81

Authors

Guo, Z.,Gourdon, P.,Wang, K. (deposition date: 2023-08-15, release date: 2024-06-26)

Primary citation

Guo, Z.,Oradd, F.,Bagenholm, V.,Gronberg, C.,Ma, J.F.,Ott, P.,Wang, Y.,Andersson, M.,Pedersen, P.A.,Wang, K.,Gourdon, P.
Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases.
Nat Commun, 15:2690-2690, 2024

PubMed Abstract: Copper transporting P-type (P-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P-ATPases remains poorly understood. In particular, the role of the intrinsic metal binding domains (MBDs) is enigmatic. Here, four cryo-EM structures and molecular dynamics simulations of a P-ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD, serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD, MBD, likely assists in copper delivery to the ATPase core. Invariant Tyr, Asn and Ser residues in the transmembrane domain assist in positioning sulfur-providing copper-binding amino acids, allowing for copper uptake, binding and release. As such, our findings unify previously conflicting data on the transport and regulation of P-ATPases. The results are critical for a fundamental understanding of cellular copper homeostasis and for comprehension of the molecular bases of P-disorders and ongoing clinical trials.

PubMed: 38538615
DOI: 10.1038/s41467-024-47001-4

Experimental method

ELECTRON MICROSCOPY (3.2 Å)