Calcium uptake protein 1

Structure)

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Micu 1 (Mitochondrial Calcium Uptake 1) is a key regulator of mitochondrial calcium uniporter (MCU) required to increase calcium uptake by MCU when cytoplasmic calcium is high. It also regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake.

Function

Micu 1 is a regulator of Ca 2+ uptakes in mitochondria. It mainly acts on MCU when linked to MICU2 (paralogues). When in an hexameric conformation : Micu 1 silences the activity of MCU/EMRE and so stop the Ca 2+ from entering the mitochondria. When the calcium of the intermembrane binds to MICU1 and MICU2 they change their conformation and open the “gate” in front of the MCU channel and let the calcium enter into the matrix.

Disease

The major disease linked to a dysfunctional Micu 1 protein is myopathy with extrapyramidal signs (MPXPS). But other diseases can be observed like : ataxia, microcephaly, ophthalmoplegia, ptosis, optic atrophy and axonal peripheral neuropathy

Structural highlights

The protein has a rich secondary structure. It has alpha helix, beta sheets and loops. Ca 2+ binds to EF domain on MICU 1 and 2 In this figure,the EF domains of the hexametric MICU 1 protein are shown in purple. Here is the binding site of calcium in the dimeric MICU 1 conformation.

See Also

https://www.rcsb.org/pdb/gene/MCU https://www.rcsb.org/pdb/gene/MICU2

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Alexandra Helleux, Michal Harel, Jaime Prilusky