6le5
From Proteopedia
Crystal structure of the mitochondrial calcium uptake 1 and 2 heterodimer (MICU1-MICU2 heterodimer) in an apo state
Structural highlights
FunctionMICU1_HUMAN Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low. Acts as a gatekeeper that senses calcium level via its EF-hand domains and sets a threshold for mitochondrial calcium uptake by MCU, thereby preventing mitochondrial calcium overload. Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake. Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG.[1] [2] [3] [4] Publication Abstract from PubMedMitochondrial calcium uptake proteins 1 and 2 (MICU1 and MICU2) mediate mitochondrial Ca(2+) influx via the mitochondrial calcium uniporter (MCU). Its molecular action for Ca(2+) uptake is tightly controlled by the MICU1-MICU2 heterodimer, which comprises Ca(2+) sensing proteins which act as gatekeepers at low [Ca(2+)] or facilitators at high [Ca(2+)]. However, the mechanism underlying the regulation of the Ca(2+) gatekeeping threshold for mitochondrial Ca(2+) uptake through the MCU by the MICU1-MICU2 heterodimer remains unclear. In this study, we determined the crystal structure of the apo form of the human MICU1-MICU2 heterodimer that functions as the MCU gatekeeper. MICU1 and MICU2 assemble in the face-to-face heterodimer with salt bridges and me-thio-nine knobs stabilizing the heterodimer in an apo state. Structural analysis suggests how the heterodimer sets a higher Ca(2+) threshold than the MICU1 homodimer. The structure of the heterodimer in the apo state provides a framework for understanding the gatekeeping role of the MICU1-MICU2 heterodimer. Structure of the MICU1-MICU2 heterodimer provides insights into the gatekeeping threshold shift.,Park J, Lee Y, Park T, Kang JY, Mun SA, Jin M, Yang J, Eom SH IUCrJ. 2020 Feb 27;7(Pt 2):355-365. doi: 10.1107/S2052252520001840. eCollection, 2020 Mar 1. PMID:32148862[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Eom SH | Jin M | Kang JY | Lee Y | Park J | Park T | Yang J
