4XTB

Crystal structure of the N-terminal domain of the human mitochondrial calcium uniporter

Summary for 4XTB

• Entry DOI: 10.2210/pdb4xtb/pdb
• Related: 4XSJ
• Descriptor: Calcium uniporter protein, mitochondrial, TETRAETHYLENE GLYCOL (3 entities in total)
• Functional Keywords: calcium channel, membrane protein, mitochondria, transport protein
• Biological source: Homo sapiens (Human)
• Cellular location: Mitochondrion inner membrane ; Multi-pass membrane protein : Q8NE86
• Total number of polymer chains: 1
• Total formula weight: 14279.37

Authors

Lee, Y.,Min, C.K.,Kim, T.G.,Song, H.K.,Lim, Y.,Kim, D.,Shin, K.,Kang, M.,Kang, J.Y.,Youn, H.-S.,Lee, J.-G.,An, J.Y.,Park, K.R.,Lim, J.J.,Kim, J.H.,Kim, J.H.,Park, Z.Y.,Kim, Y.-S.,Wang, J.,Kim, D.H.,Eom, S.H. (deposition date: 2015-01-23, release date: 2015-09-16, Last modification date: 2023-11-08)

Primary citation

Lee, Y.,Min, C.K.,Kim, T.G.,Song, H.K.,Lim, Y.,Kim, D.,Shin, K.,Kang, M.,Kang, J.Y.,Youn, H.S.,Lee, J.G.,An, J.Y.,Park, K.R.,Lim, J.J.,Kim, J.H.,Kim, J.H.,Park, Z.Y.,Kim, Y.S.,Wang, J.,Kim, D.H.,Eom, S.H.
Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter.
Embo Rep., 16:1318-1333, 2015

PubMed 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 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 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.

PubMed: 26341627
DOI: 10.15252/embr.201540436

Experimental method

X-RAY DIFFRACTION (1.5 Å)