Molecular Basis of MgATP Selectivity of the Mitochondrial SCaMC Carrier

Changqing Run; Qin Yang; Zhijun Liu; Bo OuYang; James J Chou

doi:10.1016/j.str.2015.06.004

Molecular Basis of MgATP Selectivity of the Mitochondrial SCaMC Carrier

Structure. 2015 Aug 4;23(8):1394-1403. doi: 10.1016/j.str.2015.06.004. Epub 2015 Jul 9.

Authors

Changqing Run¹, Qin Yang², Zhijun Liu³, Bo OuYang⁴, James J Chou⁵

Affiliations

¹ 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.
² Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
³ National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
⁴ 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: [email protected].
⁵ 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: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / chemistry*
Amino Acid Sequence
Antiporters / chemistry*
Antiporters / genetics
Binding Sites
Calcium-Binding Proteins / chemistry*
Calcium-Binding Proteins / genetics
Cloning, Molecular
Crystallography, X-Ray
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression
Humans
Mitochondria / chemistry*
Mitochondria / metabolism
Mitochondrial ADP, ATP Translocases / chemistry*
Mitochondrial ADP, ATP Translocases / genetics
Mitochondrial Proteins / chemistry*
Mitochondrial Proteins / genetics
Models, Molecular
Molecular Sequence Data
Mutation
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Proteolipids / chemistry
Proteolipids / metabolism
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Sequence Alignment

Substances

Antiporters
Calcium-Binding Proteins
Mitochondrial Proteins
Proteolipids
Recombinant Fusion Proteins
SLC25A24 protein, human
proteoliposomes
Adenosine Triphosphate
Mitochondrial ADP, ATP Translocases

Abstract

Publication types

MeSH terms

Substances

Grants and funding