The MCU and MCUb amino-terminal domains tightly interact: mechanisms for low conductance assembly of the mitochondrial calcium uniporter complex.

ABSTRACT: The mitochondrial calcium (Ca²⁺) uniporter (MCU) complex is regulated via integration of the MCU dominant negative beta subunit (MCUb), a low conductance paralog of the main MCU pore forming protein. The MCU amino (N)-terminal domain (NTD) also modulates channel function through cation binding to the MCU regulating acidic patch (MRAP). MCU and MCUb have high sequence similarities, yet the structural and functional roles of MCUb-NTD remain unknown. Here, we report that MCUb-NTD exhibits α-helix/β-sheet structure with a high thermal stability, dependent on protein concentration. Remarkably, MCU- and MCUb-NTDs heteromerically interact with ∼nM affinity, increasing secondary structure and stability and structurally perturbing MRAP. Further, we demonstrate MCU and MCUb co-localizatio

SUBMITTER: Noble M 

PROVIDER: S-EPMC11068563 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature