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Structure and function of the N‐terminal domain of the human mitochondrial calcium uniporter
Author(s) -
Lee Youngjin,
Min Choon Kee,
Kim Tae Gyun,
Song Hong Ki,
Lim Yunki,
Kim Dongwook,
Shin Kahee,
Kang Moonkyung,
Kang Jung Youn,
Youn HyungSeop,
Lee JungGyu,
An Jun Yop,
Park Kyoung Ryoung,
Lim Jia Jia,
Kim Ji Hun,
Kim Ji Hye,
Park Zee Yong,
Kim YeonSoo,
Wang Jimin,
Kim Do Han,
Eom Soo Hyun
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540436
Subject(s) - gist , library science , medicine , computer science , cancer research , stromal cell
Abstract The mitochondrial calcium uniporter ( MCU ) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti‐/pro‐apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N‐terminal domain ( NTD ) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted Ca MKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake‐1 and mitochondrial calcium uptake‐2 proteins ( MICU 1 and MICU 2) are not affected by the deletion of MCU NTD . However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca 2+ uptake in a stable MCU knockdown HeLa cell line and exerted dominant‐negative effects in the wild‐type MCU ‐expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.