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TitleStructural and mutational insights define ERMA as the ER Mg ATPase and reservoir gatekeeper.
Journal, issue, pagesSci Adv, Vol. 12, Issue 27, Page eaef4971, Year 2026
Publish dateJul 3, 2026
AuthorsManigandan Venkatesan / Michael L Oldham / Ning Shi / Adhishree Chidambaram / Neelanjan Vishnu / Abitha K Madesh / Kristen Bentz / Peter B Stathopulos / Ravi C Kalathur / Youxing Jiang / Muniswamy Madesh /
PubMed AbstractMagnesium (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 ...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.
External linksSci Adv / PubMed:42384784 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.2 Å
Structure data

73556

9ywq

EMDB-73556, PDB-9ywq:
the structure of ERMA complex with ATPrS and Mg++
Method: EM (single particle) / Resolution: 3.2 Å

73630

9yyd

EMDB-73630, PDB-9yyd:
the structure of ERMA Mg2+ bound form
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

ChemComp-D10:
DECANE

ChemComp-D12:
DODECANE

ChemComp-OCT:
N-OCTANE

ChemComp-PEV:
(1S)-2-{[(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE / POPE, phospholipid*YM

Source
  • mus musculus (house mouse)
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / P-type ATPase like protein

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