9YYD

the structure of ERMA Mg2+ bound form

Summary for 9YYD

• Entry DOI: 10.2210/pdb9yyd/pdb
• EMDB information: 73630
• Descriptor: Isoform 3 of Transmembrane protein 94, MAGNESIUM ION, (1S)-2-{[(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE (3 entities in total)
• Functional Keywords: p-type atpase like protein, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 154316.11

Authors

Shi, N.,Jiang, Y. (deposition date: 2025-10-28, release date: 2026-09-02)

Primary citation

Venkatesan, M.,Oldham, M.L.,Shi, N.,Chidambaram, A.,Vishnu, N.,Madesh, A.K.,Bentz, K.,Stathopulos, P.B.,Kalathur, R.C.,Jiang, Y.,Madesh, M.
Structural and mutational insights define ERMA as the ER Mg 2+ ATPase and reservoir gatekeeper.
Sci Adv, 12:eaef4971-eaef4971, 2026

PubMed Abstract: Magnesium (Mg) is the most abundant divalent cation in cells, yet the mechanisms mediating its organellar transport remain poorly defined. We identify endoplasmic reticulum (ER) Mg adenosine triphosphatase (ATPase) (ERMA) as the transporter that drives Mg 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 storage and robust adenosine 5'-triphosphate-dependent Mg 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 via the unique PILP backbone and the TM5 residue Q1110, whose mutation markedly impairs ERMA-mediated Mg uptake. Functional reconstitution of domain mutants, ERMA-SERCA chimeras, and pathogenic variants confirm ERMA as an ER-resident Mg pump and gatekeeper of ER Mg ionic equilibrium.

PubMed: 42384784
DOI: 10.1126/sciadv.aef4971

Experimental method

ELECTRON MICROSCOPY (2.8 Å)