Journal
CELL
Volume 177, Issue 5, Pages 1252-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.03.050
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Funding
- CPRIT Core Facility Support Award [RP170644]
- Howard Hughes Medical Institute
- NIH [GM079179]
- Welch Foundation [I-1578]
- Cancer Prevention and Research Institute of Texas
- Virginia Murchison Linthicum Scholar in Medical Research fund
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Mitochondrial calcium uptake is crucial to the regulation of eukaryotic Ca2+ homeostasis and is mediated by the mitochondrial calcium uniporter (MCU). While MCU alone can transport Ca2+ in primitive eukaryotes, metazoans require an essential single membrane-spanning auxiliary component called EMRE to form functional channels; however, the molecular mechanism of EMRE regulation remains elusive. Here, we present the cryo-EM structure of the human MCU-EMRE complex, which defines the interactions between MCU and EMRE as well as pinpoints the juxtamembrane loop of MCU and extended linker of EMRE as the crucial elements in the EMRE-dependent gating mechanism among metazoan MCUs. The structure also features the dimerization of two MCU-EMRE complexes along an interface at the N-terminal main (NTD) of human MCU that is a hotspot for post-translational modifications. Thus, the human MCU-EMRE complex, which constitutes the minimal channel components among metazoans, provides a framework for future mechanistic studies on MCU.
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