scholarly journals Structural Characterization of the N-Terminal Domain of the Dictyostelium discoideum Mitochondrial Calcium Uniporter

ACS Omega ◽  
2020 ◽  
Vol 5 (12) ◽  
pp. 6452-6460 ◽  
Author(s):  
Yuan Yuan ◽  
Chan Cao ◽  
Maorong Wen ◽  
Min Li ◽  
Ying Dong ◽  
...  
2019 ◽  
Author(s):  
Yuan Yuan ◽  
Chan Cao ◽  
Maorong Wen ◽  
Min Li ◽  
Ying Dong ◽  
...  

AbstractThe mitochondrial calcium uniporter (MCU) plays a critical role in the mitochondrial calcium uptake into the matrix. In metazoans, the uniporter is a tightly regulated multi-component system including the pore-forming subunit MCU and several regulators (MICU1, MICU2, EMRE). The calcium-conducting activity of metazoan MCU requires the single-transmembrane protein EMRE. Dictyostelium discoideum (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 homologs. Biochemical and biophysical analyses of DdMCU-NTD in solution indicated that the domain exists as oligomers, most probably as a pentamer or hexamer. Mutagenesis showed that the acidic residues Asp60, Glu72 and Glu74, which appeared to mediate the parallel interface as observed in the crystal structure, participated in the self-assembly of DdMCU-NTD. Intriguingly, the oligomeric complex readily dissociated to lower-order oligomers 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.


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Author(s):  
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V. P. Kutyshenko ◽  
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...  

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Vol 106 (2) ◽  
pp. 760a
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Enrico Teardo ◽  
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Author(s):  
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EMBO Reports ◽  
2015 ◽  
Vol 16 (10) ◽  
pp. 1318-1333 ◽  
Author(s):  
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Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 288-LB
Author(s):  
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...  

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