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Structural Mechanism of EMRE-Dependent Gating of the Human Mitochondrial Calcium Uniporter.

Cell (2019-05-14)
Yan Wang, Nam X Nguyen, Ji She, Weizhong Zeng, Yi Yang, Xiao-Chen Bai, Youxing Jiang
ABSTRACT

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 domain (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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium butyrate, 98%
Sigma-Aldrich
Cholesteryl hemisuccinate
Sigma-Aldrich
Cholesteryl hemisuccinate tris salt, anionic detergent
Sigma-Aldrich
Indole-3-butyric acid potassium salt, suitable for plant cell culture, BioReagent
Sigma-Aldrich
Anti-MCU antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution