5Z2H

Structure of Dictyostelium discoideum mitochondrial calcium uniporter N-terminal domain(DdMCU-NTD)

Summary for 5Z2H

• Entry DOI: 10.2210/pdb5z2h/pdb
• Descriptor: Dictyostelium discoideum mitochondrial calcium uniporter (2 entities in total)
• Functional Keywords: membrane protein
• Biological source: Dictyostelium discoideum (Slime mold)
• Total number of polymer chains: 2
• Total formula weight: 23566.84

Authors

Yuan, Y.,Wen, M.,Chou, J.J.,Li, D.,Bo, O. (deposition date: 2018-01-02, release date: 2019-01-02, Last modification date: 2024-03-27)

Primary citation

Yuan, Y.,Cao, C.,Wen, M.,Li, M.,Dong, Y.,Wu, L.,Wu, J.,Cui, T.,Li, D.,Chou, J.J.,OuYang, B.
Structural Characterization of the N-Terminal Domain of theDictyostelium discoideumMitochondrial Calcium Uniporter.
Acs Omega, 5:6452-6460, 2020

PubMed Abstract: The mitochondrial calcium uniporter (MCU) plays a critical role in mitochondrial calcium uptake into the matrix. In metazoans, the uniporter is a tightly regulated multicomponent system, including the pore-forming subunit MCU and several regulators (MICU1, MICU2, and Essential MCU REgulator, EMRE). The calcium-conducting activity of metazoan MCU requires the single-transmembrane protein EMRE. (Dd), however, developed a simplified uniporter for which the pore-forming MCU (DdMCU) alone is necessary and sufficient for calcium influx. Here, we report a crystal structure of the N-terminal domain (NTD) of DdMCU at 1.7 Å resolution. The DdMCU-NTD contains four helices and two strands arranged in a fold that is completely different from the known structures of other MCU-NTD homologues. Biochemical and biophysical analyses of DdMCU-NTD in solution indicated that the domain exists as high-order oligomers. Mutagenesis showed that the acidic residues Asp60, Glu72, and Glu74, which appeared to mediate the interface II, as observed in the crystal structure, participated in the self-assembly of DdMCU-NTD. Intriguingly, the oligomeric complex was disrupted in the presence of calcium. We propose that the calcium-triggered dissociation of NTD regulates the channel activity of DdMCU by a yet unknown mechanism.

PubMed: 32258880
DOI: 10.1021/acsomega.9b04045

Experimental method

X-RAY DIFFRACTION (1.674 Å)