8q76
Copper-transporting ATPase HMA4 in E2P state with BeFCopper-transporting ATPase HMA4 in E2P state with BeF
Structural highlights
FunctionHMA4_ORYSJ Copper (Cu) transporter that mediates Cu transport in root vacuoles. Involved in Cu detoxification by sequestrating Cu into root vacuoles and limiting translocation of Cu from the roots to the shoots, and accumulation in grains.[1] Publication Abstract from PubMedCopper transporting P-type (P(1B-1)-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P(1B-1)-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(1B-1)-ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD(-1), serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD(-1), MBD(-2), 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(1B-1)-ATPases. The results are critical for a fundamental understanding of cellular copper homeostasis and for comprehension of the molecular bases of P(1B-1)-disorders and ongoing clinical trials. Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases.,Guo Z, Oradd F, Bagenholm V, Gronberg C, Ma JF, Ott P, Wang Y, Andersson M, Pedersen PA, Wang K, Gourdon P Nat Commun. 2024 Mar 27;15(1):2690. doi: 10.1038/s41467-024-47001-4. PMID:38538615[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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