6eaz

Apo structure of the mitochondrial calcium uniporter protein MICU2

spinqualitylabelsall models 6eaz, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6eaz is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL Gene: Micu2, Efha1 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MICU2_MOUSE] Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:23409044, PubMed:24560927). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting Ca(2+), avoiding energy dissipation and cell-death triggering (PubMed:24560927). Publication Abstract from PubMed The mitochondrial uniporter is a Ca(2+)-channel complex resident within the organelle's inner membrane. In mammalian cells the uniporter's activity is regulated by Ca(2+) due to concerted action of MICU1 and MICU2, two paralogous, but functionally distinct, EF-hand Ca(2+)-binding proteins. Here we present the X-ray structure of the apo form of Mus musculus MICU2 at 2.5-A resolution. The core structure of MICU2 is very similar to that of MICU1. It consists of two lobes, each containing one canonical Ca(2+)-binding EF-hand (EF1, EF4) and one structural EF-hand (EF2, EF3). Two molecules of MICU2 form a symmetrical dimer stabilized by highly conserved hydrophobic contacts between exposed residues of EF1 of one monomer and EF3 of another. Similar interactions stabilize MICU1 dimers, allowing exchange between homo- and heterodimers. The tight EF1-EF3 interface likely accounts for the structural and functional coupling between the Ca(2+)-binding sites in MICU1, MICU2, and their complex that leads to the previously reported Ca(2+)-binding cooperativity and dominant negative effect of mutation of the Ca(2+)-binding sites in either protein. The N- and C-terminal segments of the two proteins are distinctly different. In MICU2 the C-terminal helix is significantly longer than in MICU1, and it adopts a more rigid structure. MICU2's C-terminal helix is dispensable in vitro for its interaction with MICU1 but required for MICU2's function in cells. We propose that in the MICU1-MICU2 oligomeric complex the C-terminal helices of both proteins form a central semiautonomous assembly which contributes to the gating mechanism of the uniporter. Crystal structure of MICU2 and comparison with MICU1 reveal insights into the uniporter gating mechanism.,Kamer KJ, Jiang W, Kaushik VK, Mootha VK, Grabarek Z Proc Natl Acad Sci U S A. 2019 Feb 12. pii: 1817759116. doi:, 10.1073/pnas.1817759116. PMID:30755530 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Calcium uptake protein 3D structures

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