Structure of the MICU1–MICU2 heterodimer provides insights into the gatekeeping threshold shift

Park J.; Lee Y.; Park T.Kang J.Y.Mun S.A.Jin M.Yang J.Eom S.H.

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Structure of the MICU1–MICU2 heterodimer provides insights into the gatekeeping threshold shift

机译：Structure of the MICU1–MICU2 heterodimer provides insights into the gatekeeping threshold shift

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Mitochondrial calcium uptake proteins 1 and 2 (MICU1 and MICU2) mediate mitochondrial Ca2+ influx via the mitochondrial calcium uniporter (MCU). Its molecular action for Ca2+ uptake is tightly controlled by the MICU1–MICU2 heterodimer, which comprises Ca2+ sensing proteins which act as gatekeepers at low Ca2+ or facilitators at high Ca2+. However, the mechanism underlying the regulation of the Ca2+ gatekeeping threshold for mitochondrial Ca2+ 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 methionine knobs stabilizing the heterodimer in an apo state. Structural analysis suggests how the heterodimer sets a higher Ca2+ 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.

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《iucrj》 |2020年第2期|355-365|共11页
作者
Park J.; Lee Y.; Park T.Kang J.Y.Mun S.A.Jin M.Yang J.Eom S.H.;
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School of Life Sciences, Gwangju Institute of Science and Technology (GIST);

Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST);

Infection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Department of Chemistry, Gwangju Institute of Science and Technology (GIST);

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正文语种英语
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MITOCHONDRIAL CALCIUM UPTAKE; MICU1-MICU2 HETERODIMER; MCU GATEKEEPERS; COOPERATIVITY; CA2+ SENSING PROTEINS; X-RAY CRYSTALLOGRAPHY;

Structure of the MICU1–MICU2 heterodimer provides insights into the gatekeeping threshold shift

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