Structure and function of the N‐terminal domain of the human mitochondrial calcium uniporter
| Autor: | Kahee Shin, Hong Ki Song, Kyoung Ryoung Park, Choon Kee Min, Yeon-Soo Kim, Jimin Wang, Zee Yong Park, Ji Hun Kim, Moonkyung Kang, Hyung-Seop Youn, Youngjin Lee, Do Han Kim, Dongwook Kim, Jia Jia Lim, Soo Hyun Eom, Tae Gyun Kim, Yunki Lim, Jun Yop An, Jihye Kim, Jung Youn Kang, Jung-Gyu Lee |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular crystal structure Protein Folding Mutant mitochondrial calcium uptake chemistry.chemical_element uniplex Calcium Mitochondrion Biology Crystallography X-Ray Mitochondrial Membrane Transport Proteins Biochemistry Article Protein Structure Secondary Mitochondrial membrane transport protein Structural Biology Calcium-binding protein Genetics Humans Protein Interaction Domains and Motifs Mitochondrial calcium uptake Membrane & Intracellular Transport Molecular Biology Voltage-dependent calcium channel Calcium-Binding Proteins HEK 293 cells Articles Mitochondria Protein Structure Tertiary Cell biology MCU HEK293 Cells chemistry MCU domain‐like fold Mutation biology.protein Calcium Channels HeLa Cells |
| Zdroj: | EMBO Reports |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201540436 |
| Popis: | 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 CaMKII 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 (MICU1 and MICU2) 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 Ca2+ 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. |
| Databáze: | OpenAIRE |
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