The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter.

ABSTRACT: The MICU1-MICU2 heterodimer regulates the mitochondrial calcium uniporter (MCU) and mitochondrial calcium uptake. Herein, we present two crystal structures of the MICU1-MICU2 heterodimer, in which Ca²⁺ -free and Ca²⁺ -bound EF-hands are observed in both proteins, revealing both electrostatic and hydrophobic interfaces. Furthermore, we show that MICU1 interacts with EMRE, another regulator of MCU, through a Ca²⁺ -dependent alkaline groove. Ca²⁺ binding strengthens the MICU1-EMRE interaction, which in turn facilitates Ca²⁺ uptake. Conversely, the MICU1-MCU interaction is favored in the absence of Ca²⁺ , thus inhibiting the channel activity. This Ca²⁺ -dependent switch illuminates how calcium signals are transmitted

SUBMITTER: Wu W 

PROVIDER: S-EPMC7527922 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature