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The Mitochondrial Calcium Uniporter Is Autoregulated By Cation Binding To The Β-Grasp-Like Matrix Domain, Samuel K. Lee

Electronic Thesis and Dissertation Repository

Mitochondrial calcium (Ca²⁺) uptake plays fundamental roles in various signaling processes. Entry of Ca²⁺ into the mitochondrial matrix is tightly controlled by the mitochondrial Ca²⁺ uniporter (MCU) in a higher order complex regulated by inter- and intra-molecular protein-protein interactions. However, the precise mechanisms controlling MCU function and regulation remain largely unknown. I identified a well-folded N-terminal MCU region from residues 72-189, and its crystal structure revealed a β-grasp-like fold with a cluster of acidic residues that facilitates interactions with dibasic cations. Binding of Ca²⁺ or Mg²⁺ destabilize this fold and shift the protein towards …