6LB7

Crystal structure of the Ca2+-free and Ca2+-bound MICU1-MICU2 complex

Summary for 6LB7

• Entry DOI: 10.2210/pdb6lb7/pdb
• Descriptor: Calcium uptake protein 1, mitochondrial, Calcium uptake protein 2, mitochondrial, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: calcium binding protein, mitochondrial, uniporter, ef-hand, metal binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 163686.54

Authors

Wu, W.,Shen, Q.,Zheng, J.,Jia, Z. (deposition date: 2019-11-13, release date: 2020-07-15, Last modification date: 2023-11-22)

Primary citation

Wu, W.,Shen, Q.,Zhang, R.,Qiu, Z.,Wang, Y.,Zheng, J.,Jia, Z.
The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter.
Embo J., 39:e104285-e104285, 2020

PubMed 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 Ca -free and Ca -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 Ca -dependent alkaline groove. Ca binding strengthens the MICU1-EMRE interaction, which in turn facilitates Ca uptake. Conversely, the MICU1-MCU interaction is favored in the absence of Ca , thus inhibiting the channel activity. This Ca -dependent switch illuminates how calcium signals are transmitted from regulatory subunits to the calcium channel and the transition between gatekeeping and activation channel functions. Furthermore, competition with an EMRE peptide alters the uniporter threshold in resting conditions and elevates Ca accumulation in stimulated mitochondria, confirming the gatekeeper role of the MICU1-MICU2 heterodimer. Taken together, these structural and functional data provide new insights into the regulation of mitochondrial calcium uptake.

PubMed: 32790952
DOI: 10.15252/embj.2019104285

Experimental method

X-RAY DIFFRACTION (2.101 Å)