9MT7

Cryo-EM Structure of the Magnesium Transporter MgtA in the E2 Conformation Bound to Mg2+

Summary for 9MT7

• Entry DOI: 10.2210/pdb9mt7/pdb
• EMDB information: 48602
• Descriptor: Magnesium-transporting ATPase, P-type 1, MAGNESIUM ION (2 entities in total)
• Functional Keywords: p-type atpase, metal transport, transport protein
• Biological source: Lactococcus lactis subsp. lactis
• Total number of polymer chains: 1
• Total formula weight: 99374.56

Authors

Khan, M.B.,Primeau, J.O.,Basu, P.C.,Morth, J.P.,Lemieux, M.J.,Young, H.S. (deposition date: 2025-01-10, release date: 2026-01-21, Last modification date: 2026-06-24)

Primary citation

Khan, M.B.,Primeau, J.O.,Chaudhuri-Basu, P.,Bergdoll, L.,Renault, L.,Morth, J.P.,Lemieux, M.J.,Young, H.S.
Distinct transport cycle and lipid regulation of a Mg 2+ -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, Mg is of critical importance in bacterial, fungal, and plant cellular homeostasis. A bacterial P-type ATPase found in Gram-negative bacteria, Mg transporter A (MgtA), facilitates the transport of Mg from the periplasm to the cytoplasm under conditions of Mg starvation. MgtA is a cardiolipin-sensitive integral membrane ion-transporter that scavenges Mg during bacterial infection and pathogenesis. Here, we determined cryo-EM structures of MgtA capturing three distinct states along the Mg 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 Mg in the transmembrane domain coordinated in a novel site involving Ser and Asn on M5, Ser and Asp on M7, and Ser and Thr on M8. In the E2-P conformation, the phosphate analog BeF is bound in close proximity to the catalytic aspartate, Asp, suggesting that it represents a covalent aspartylphosphate intermediate. In the presence of AMPPCP, Mg 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

ELECTRON MICROSCOPY (3.23 Å)