6C5R

Crystal structure of the soluble domain of the mitochondrial calcium uniporter

Summary for 6C5R

• Entry DOI: 10.2210/pdb6c5r/pdb
• Descriptor: calcium uniporter (1 entity in total)
• Functional Keywords: cytosolic protein
• Biological source: Metarhizium acridum (strain CQMa 102); More
• Total number of polymer chains: 8
• Total formula weight: 194141.41

Authors

Fan, C.,Fan, M.,Fastman, N.,Zhang, J.,Feng, L. (deposition date: 2018-01-16, release date: 2018-07-11, Last modification date: 2024-03-13)

Primary citation

Fan, C.,Fan, M.,Orlando, B.J.,Fastman, N.M.,Zhang, J.,Xu, Y.,Chambers, M.G.,Xu, X.,Perry, K.,Liao, M.,Feng, L.
X-ray and cryo-EM structures of the mitochondrial calcium uniporter.
Nature, 559:575-579, 2018

PubMed Abstract: Mitochondrial calcium uptake is critical for regulating ATP production, intracellular calcium signalling, and cell death. This uptake is mediated by a highly selective calcium channel called the mitochondrial calcium uniporter (MCU). Here, we determined the structures of the pore-forming MCU proteins from two fungi by X-ray crystallography and single-particle cryo-electron microscopy. The stoichiometry, overall architecture, and individual subunit structure differed markedly from those described in the recent nuclear magnetic resonance structure of Caenorhabditis elegans MCU. We observed a dimer-of-dimer architecture across species and chemical environments, which was corroborated by biochemical experiments. Structural analyses and functional characterization uncovered the roles of key residues in the pore. These results reveal a new ion channel architecture, provide insights into calcium coordination, selectivity and conduction, and establish a structural framework for understanding the mechanism of mitochondrial calcium uniporter function.

PubMed: 29995856
DOI: 10.1038/s41586-018-0330-9

Experimental method

X-RAY DIFFRACTION (3.09608311048 Å)