Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters

Article

关键词: CRYSTAL-STRUCTURE;    ESSENTIAL COMPONENT;    POTASSIUM CHANNEL;    K+ CHANNEL;    MEMBRANE;    PROTEIN;    MCUR1;    ANTIBODIES;    REGULATOR;    COMPLEX;   

DOI  :  10.1038/s41586-018-0331-8

来源: SCIE

【 摘 要 】

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 angstrom and 3.2 angstrom 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.

【 授权许可】

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