Structural insights into the Ca2+-dependent gating of the human mitochondrial calcium uniporter
Autor: | Yan Wang, Yan Han, Ji She, Nam X Nguyen, Vamsi K Mootha, Xiao-chen Bai, Youxing Jiang |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: | |
Zdroj: | eLife, Vol 9 (2020) |
Druh dokumentu: | article |
ISSN: | 2050-084X |
DOI: | 10.7554/eLife.60513 |
Popis: | Mitochondrial Ca2+ uptake is mediated by an inner mitochondrial membrane protein called the mitochondrial calcium uniporter. In humans, the uniporter functions as a holocomplex consisting of MCU, EMRE, MICU1 and MICU2, among which MCU and EMRE form a subcomplex and function as the conductive channel while MICU1 and MICU2 are EF-hand proteins that regulate the channel activity in a Ca2+-dependent manner. Here, we present the EM structures of the human mitochondrial calcium uniporter holocomplex (uniplex) in the presence and absence of Ca2+, revealing distinct Ca2+ dependent assembly of the uniplex. Our structural observations suggest that Ca2+ changes the dimerization interaction between MICU1 and MICU2, which in turn determines how the MICU1-MICU2 subcomplex interacts with the MCU-EMRE channel and, consequently, changes the distribution of the uniplex assemblies between the blocked and unblocked states. |
Databáze: | Directory of Open Access Journals |
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