9EJN

Crystal structure of magnesium-transporting ATPase MgtA in an E1-like magnesium-bound state

Summary for 9EJN

• Entry DOI: 10.2210/pdb9ejn/pdb
• Descriptor: Magnesium-transporting ATPase, P-type 1, MAGNESIUM ION (2 entities in total)
• Functional Keywords: metal transport, membrane protein, p-type atpase, magnesium ion
• Biological source: Lactococcus lactis subsp. lactis CV56
• Total number of polymer chains: 4
• Total formula weight: 406112.84

Authors

Khan, M.B.,Primeau, J.O.,Basu, P.C.,Morth, J.P.,Lemieux, M.J.,Young, H.S. (deposition date: 2024-11-28, release date: 2025-02-26, Last modification date: 2026-06-10)

Primary citation

Young, H.,Khan, M.B.,Primeau, J.,Chaudhuri-Basu, P.,Bergdoll, L.,Renault, L.,Morth, J.P.,Lemieux, M.J.
Distinct transport cycle and lipid regulation of a Mg2+-transporting P-type ATPase, MgtA.
Res Sq, 2026

PubMed Abstract: P-type ATPases represent an evolutionarily conserved superfamily of ion, lipid, and peptide pumps found across all domains of life. Among the substrates transported by P-type ATPases, Mg2+ is of critical importance in bacterial, fungal, and plant cellular homeostasis. A bacterial P-type ATPase found in Gram-negative bacteria, Mg2+ transporter A (MgtA), facilitates the transport of Mg2+ from the periplasm to the cytoplasm under conditions of Mg2+ starvation. MgtA is a cardiolipin-sensitive integral membrane ion-transporter that scavenges Mg2+ during bacterial infection and pathogenesis. Here, we determined cryo-EM structures of MgtA capturing three distinct states along the Mg2+ transport cycle, including a phosphorylated E2-P intermediate (2.6 Å resolution), an E1-like conformation stabilized by the peptide regulator MgtR (2.7 Å resolution), and an E1-like ATP-bound state (2.8 Å resolution). These three conformations reveal the binding of Mg2+ in the transmembrane domain coordinated in a novel site involving Ser702 and Asn706 on M5, Ser773 and Asp777 on M7, and Ser821 and Thr824 on M8. In the E2-P conformation, the phosphate analog BeF3 is bound in close proximity to the catalytic aspartate, Asp361, suggesting that it represents a covalent aspartylphosphate intermediate. In the presence of AMPPCP, Mg2+ remains bound in the transmembrane domain and the ATP analog is bound in a catalytically competent conformation. Overall, the structures reveal distinct steps in the transport cycle of MgtA compared to other P-type ATPases, as well as lipid binding sites that fill gaps in our understanding of transport regulation.

PubMed: 42147146
DOI: 10.21203/rs.3.rs-9173029/v1

Experimental method

X-RAY DIFFRACTION (3.55 Å)