title: Molecular Basis of MgATP Selectivity of the Mitochondrial SCaMC Carrier.
abstract: The mitochondrial matrix is the supplier of cellular ATP. The short Ca(2+)-binding mitochondrial carrier (SCaMC) is one of the two mitochondrial carriers responsible for transporting ATP across the mitochondrial inner membrane. While the ADP/ATP carrier (AAC) accounts for the bulk ADP/ATP recycling in the matrix, the function of SCaMC is important for mitochondrial activities that depend on adenine nucleotides, such as gluconeogenesis and mitochondrial biogenesis. A key difference between SCaMC and AAC is that SCaMC selectively transports MgATP whereas AAC only transports free nucleotides. Here, we use a combination of nuclear magnetic resonance experiments and functional mutagenesis to investigate the structural basis of the MgATP selectivity in SCaMC. Our data revealed an MgATP binding site inside the transporter cavity, while identifying an aspartic acid residue that plays an important role in the higher selectivity for MgATP over free ATP.
authors.affiliation: National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China; State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Run
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China; State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: ouyang@sibcb.ac.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: OuYang
authors.affiliation: National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China; State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: james_chou@hms.harvard.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Chou
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D000595:Amino Acid Sequence; D017920:Antiporters / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry* / Q000235:genetics; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D017920:Antiporters; D002135:Calcium-Binding Proteins; D024101:Mitochondrial Proteins; D011510:Proteolipids; D011993:Recombinant Fusion Proteins; C487500:SLC25A24 protein, human; C020485:proteoliposomes; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases