Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters.
| Publication Type | Academic Article |
| Authors | Baradaran R, Wang C, Siliciano A, Long S |
| Journal | Nature |
| Volume | 559 |
| Issue | 7715 |
| Pagination | 580-584 |
| Date Published | 07/11/2018 |
| ISSN | 1476-4687 |
| Keywords | Calcium Channels, Cryoelectron Microscopy, Phialophora, Zebrafish |
| 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 Å and 3.2 Å 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. |
| DOI | 10.1038/s41586-018-0331-8 |
| PubMed ID | 29995857 |
| PubMed Central ID | PMC6336196 |