Cryo-EM structure of a mitochondrial calcium uniporter

Science. 2018 Aug 3;361(6401):506-511. doi: 10.1126/science.aar4056. Epub 2018 Jun 28.

Abstract

Calcium transport plays an important role in regulating mitochondrial physiology and pathophysiology. The mitochondrial calcium uniporter (MCU) is a calcium-selective ion channel that is the primary mediator for calcium uptake into the mitochondrial matrix. Here, we present the cryo-electron microscopy structure of the full-length MCU from Neurospora crassa to an overall resolution of ~3.7 angstroms. Our structure reveals a tetrameric architecture, with the soluble and transmembrane domains adopting different symmetric arrangements within the channel. The conserved W-D-Φ-Φ-E-P-V-T-Y sequence motif of MCU pore forms a selectivity filter comprising two acidic rings separated by one helical turn along the central axis of the channel pore. The structure combined with mutagenesis gives insight into the basis of calcium recognition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Calcium / metabolism*
  • Calcium Channels / chemistry*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Calcium Channels / ultrastructure
  • Conserved Sequence
  • Cryoelectron Microscopy
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Fungal Proteins / ultrastructure
  • Models, Chemical
  • Mutagenesis
  • Neurospora crassa / metabolism*
  • Protein Conformation
  • Protein Multimerization

Substances

  • Calcium Channels
  • Fungal Proteins
  • mitochondrial calcium uniporter
  • Calcium