PUBLICATION
Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters
- Authors
- Baradaran, R., Wang, C., Siliciano, A.F., Long, S.B.
- ID
- ZDB-PUB-180713-9
- Date
- 2018
- Source
- Nature 559(7715): 580-584 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Calcium Channels/chemistry*
- Calcium Channels/metabolism
- Calcium Channels/ultrastructure*
- Caenorhabditis elegans/chemistry
- Ion Channel Gating
- Cryoelectron Microscopy*
- Calcium/metabolism
- Zebrafish*
- Protein Subunits/chemistry
- Protein Subunits/metabolism
- Models, Molecular
- Phialophora/chemistry*
- Protein Multimerization
- Animals
- PubMed
- 29995857 Full text @ Nature
Citation
Baradaran, R., Wang, C., Siliciano, A.F., Long, S.B. (2018) Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters. Nature. 559(7715):580-584.
Abstract
The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel and a major route of calcium entry into mitochondria. How the channel catalyses ion permeation and achieves ion selectivity are not well understood, partly because MCU is thought to have a distinct architecture in comparison to other cellular channels. Here we report cryo-electron microscopy reconstructions of MCU channels from zebrafish and Cyphellophora europaea at 8.5 Ć and 3.2 Ć resolutions, respectively. In contrast to a previous report of pentameric stoichiometry for MCU, both channels are tetramers. The atomic model of C. europaea MCU shows that a conserved WDXXEP signature sequence forms the selectivity filter, in which calcium ions are arranged in single file. Coiled-coil legs connect the pore to N-terminal domains in the mitochondrial matrix. In C. europaea MCU, the N-terminal domains assemble as a dimer of dimers; in zebrafish MCU, they form an asymmetric crescent. The structures define principles that underlie ion permeation and calcium selectivity in this unusual channel.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping