Seminar: Rozbeh Baradaran

Sep
18
Sep/18 15:00 - Sep/18 16:00
Sackler Lecture Theatre Wellcome Trust/MRC Building
Tuesday, 18 September, 2018 - 15:00

Cryo-EM structures of the mitochondrial calcium uniporters

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. I will be presenting the cryo-electron microscopy reconstructions of MCU channels from zebrafish and Cyphellophora europaea at 8.5 angstrom and 3.2 angstrom resolutions, respectively. The small molecular weight of MCU, just approximately 110 kDa for the ordered region of the channel assembly, posed challenges for structure determination by cryo-EM, and it is one of the smallest membrane proteins to have the structure determined to atomic resolution by cryo-EM. 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.