13IO

MCU-EMRE complex with spermine

Summary for 13IO

• Entry DOI: 10.2210/pdb13io/pdb
• EMDB information: 77084
• Descriptor: Essential MCU regulator, mitochondrial, Calcium uniporter protein, mitochondrial, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: mitochondrial calcium uniporter, mcu, emre, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 114774.30

Authors

Wang, Q.,Balderas, E.,Rai, N.K.,Cao, E.,Chaudhuri, D. (deposition date: 2026-05-07, release date: 2026-07-08, Last modification date: 2026-08-12)

Primary citation

Wang, Q.,Balderas, E.,Ramos, A.J.,Nwafor, A.,McManus, J.S.,Rai, N.K.,Masini, Y.B.,Eberhardt, D.R.,Rekate, E.C.,Balynas, A.M.,Yin, X.,Stewart, T.M.,Cao, E.,Stary-Weinzinger, A.,Chaudhuri, D.
Matrix polyamines regulate bidirectional calcium flux through MCU.
Structure, 2026

PubMed Abstract: Polyamines, well-known regulators of the mitochondrial calcium (Ca) uniporter channel, show unexpected effects when binding the channel from within the matrix. Using cryo-EM, molecular dynamics simulations, and mutagenesis experiments, we determine that polyamines achieve such regulation by binding within the pore to a ring of negative residues forming a matrix gate, inhibiting Ca conduction. In whole-mitoplast electrophysiology assays, matrix polyamines cause a gradual increase in Ca currents during prolonged conduction, due to relief of this inhibition. Notably, this electrostatic binding increases 3-fold as the inner membrane depolarizes, preventing Ca efflux. Additionally, we also identify that phospholipids form part of the Ca conduction pathway through MCU. Because we find significant variability in matrix polyamine content across mouse organs, this unexpected mechanism for sculpting the mitochondrial Ca waveform suggests a tissue-specific regulation of metabolism.

PubMed: 42508402
DOI: 10.1016/j.str.2026.07.002

Experimental method

ELECTRON MICROSCOPY (2.98 Å)