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bioRxiv · 10.1101/2020.04.04.025205

Structure of intact human MCU supercomplex with the auxiliary MICU subunits

Zhuo, W.·Zhou, H.·Guo, R.·Yi, J.·Yu, L.·Sui, Y.·Zhang, L.·Zeng, W.·Wang, P.·Yang, M.
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Abstract

The mitochondrial Ca2+ uniporter (MCU) supercomplex is essential for mitochondrial Ca2+ uptake. Here, we present high-resolution cryo-EM structures of human MCU-EMRE supercomplex (MES, 3.41 [A]) and MCU-EMRE-MICU1-MICU2 supercomplex (MEMMS, 3.64 [A]). MES adopts a V-shaped dimer architecture comprising two hetero-octamers, and a pair of MICU1-MICU2 hetero-dimers form a bridge across the two halves of MES to constitute an O-shaped architecture of MEMMS. The MES and MEMMS pore profiles are almost identical, with Ca2+ in the selectivity filters and no obstructions, indicating both channels are conductive. Contrary to the current model in which MICUs block the MCU pore, MICU1-MICU2 dimers are located on the periphery of the MCU pores and do not occlude them. However, MICU1-MICU2 dimers may modulate MCU gating by affecting the matrix gate through the EMRE lever.

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Zhuo, W., Zhou, H., Guo, R., Yi, J., Yu, L., Sui, Y., Zhang, L., Zeng, W., Wang, P., Yang, M.. 2020-04-05. Structure of intact human MCU supercomplex with the auxiliary MICU subunits. https://doi.org/10.1101/2020.04.04.025205

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