title: A self-sequestered calmodulin-like Ca²⁺ sensor of mitochondrial SCaMC carrier and its implication to Ca²⁺-dependent ATP-Mg/P(i) transport.
abstract: The mitochondrial carriers play essential roles in energy metabolism. The short Ca²⁺-binding mitochondrial carrier (SCaMC) transports ATP-Mg in exchange for Pi and is important for activities that depend on adenine nucleotides. SCaMC adopts, in addition to the transmembrane domain (TMD) that transports solutes, an extramembrane N-terminal domain (NTD) that regulates solute transport in a Ca²⁺-dependent manner. Crystal structure of the Ca²⁺-bound NTD reveals a compact architecture in which the functional EF hands are sequestered by an endogenous helical segment. Nuclear magnetic resonance (NMR) relaxation rates indicated that removal of Ca²⁺ from NTD results in a major conformational switch from the rigid and compact Ca²⁺-bound state to the dynamic and loose apo state. Finally, we showed using surface plasmon resonance and NMR titration experiments that free apo NTDs could specifically interact with liposome-incorporated TMD, but that Ca²⁺ binding drastically weakened the interaction. Our results together provide a molecular explanation for Ca²⁺-dependent ATP-Mg flux in mitochondria.
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors: Qin
authors: Q
authors: Yang
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors: Sven
authors: S
authors: Brüschweiler
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: chou@cmcd.hms.harvard.edu.
authors: James J
authors: JJ
authors: Chou
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D017920:Antiporters / Q000737:chemistry* / Q000502:physiology*; D002118:Calcium / Q000737:chemistry*; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D002147:Calmodulin / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008274:Magnesium / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000502:physiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011510:Proteolipids / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D017920:Antiporters; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D024101:Mitochondrial Proteins; D010455:Peptides; D010710:Phosphates; D011510:Proteolipids; C487500:SLC25A24 protein, human; C020485:proteoliposomes; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium