Cryo-EM structure of a mitochondrial calcium uniporter

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Jiho Yoo1, Mengyu Wu2, Ying Yin1

  • 1Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.

Science (New York, N.Y.)
|June 30, 2018
PubMed

Insights

Researchers determined the structure of the mitochondrial calcium uniporter (MCU), a key channel for calcium uptake into mitochondria. This finding reveals the channel's architecture and how it recognizes calcium ions.

Area of Science:

  • Mitochondrial physiology and pathophysiology
  • Ion channel structure and function
  • Biophysics and structural biology

Background:

  • Calcium transport is crucial for mitochondrial function and disease.
  • The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix.
  • Understanding MCU structure is vital for elucidating calcium regulation mechanisms.

Purpose of the Study:

  • To determine the high-resolution cryo-electron microscopy structure of the full-length Neurospora crassa MCU.
  • To elucidate the structural basis of calcium selectivity and recognition by the MCU.
  • To provide insights into the tetrameric architecture and domain arrangements of the MCU.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) of full-length Neurospora crassa MCU.
  • High-resolution structure determination to approximately 3.7 angstroms.
  • Site-directed mutagenesis to investigate calcium recognition mechanisms.

Main Results:

  • The MCU exhibits a tetrameric architecture with distinct soluble and transmembrane domain arrangements.
  • A conserved sequence motif (W-D-Φ-Φ-E-P-V-T-Y) forms a selectivity filter within the MCU pore.
  • The selectivity filter features two acidic rings separated by one helical turn, crucial for calcium ion binding.

Conclusions:

  • The determined MCU structure provides a detailed molecular model of mitochondrial calcium uptake.
  • Structural insights reveal the mechanism of calcium ion selectivity and recognition at the channel pore.
  • This work lays the foundation for understanding MCU regulation in physiological and pathological contexts.

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