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the structure of ERMA complex with ATPrS and Mg++
Structural highlights
FunctionTMM94_MOUSE Could function in the uptake of Mg(2+) from the cytosol into the endoplasmic reticulum and regulate intracellular Mg(2+) homeostasis.[1] Publication Abstract from PubMedMagnesium (Mg(2+)) is the most abundant divalent cation in cells, yet the mechanisms mediating its organellar transport remain poorly defined. We identify endoplasmic reticulum (ER) Mg(2+) adenosine triphosphatase (ATPase) (ERMA) as the transporter that drives Mg(2+) uptake into the ER lumen, establishing the ER as a bi-ionic intracellular reservoir. MagFRET biosensors targeted to the ER demonstrate that ERMA mediates dynamic ER Mg(2+) storage and robust adenosine 5'-triphosphate-dependent Mg(2+) uptake reaching 15 to 30 millimolar. Cryo-electron microscopy structures of human and mouse ERMA reveal a P-type ATPase fold with an unwound transmembrane 4 (TM4) that coordinates Mg(2+) via the unique PILP backbone and the TM5 residue Q1110, whose mutation markedly impairs ERMA-mediated Mg(2+) uptake. Functional reconstitution of domain mutants, ERMA-SERCA chimeras, and pathogenic variants confirm ERMA as an ER-resident Mg(2+) pump and gatekeeper of ER Mg(2+) ionic equilibrium. Structural and mutational insights define ERMA as the ER Mg(2+) ATPase and reservoir gatekeeper.,Venkatesan M, Oldham ML, Shi N, Chidambaram A, Vishnu N, Madesh AK, Bentz K, Stathopulos PB, Kalathur RC, Jiang Y, Madesh M Sci Adv. 2026 Jul 3;12(27):eaef4971. doi: 10.1126/sciadv.aef4971. Epub 2026 Jul , 1. PMID:42384784[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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