title: Substrate-modulated ADP/ATP-transporter dynamics revealed by NMR relaxation dispersion.
abstract: The ADP/ATP carrier (AAC) transports ADP and ATP across the inner mitochondrial membrane. Unlike most transporters, which have two-fold direct or inverted quasisymmetry, AAC has apparent three-fold rotational symmetry. Further, its transport rate is relatively fast for transporters that carry large solutes. Here, we study the yeast AAC carrier 3 by obtaining comprehensive NMR relaxation dispersion measurements, which provide residue-specific information on the protein's conformational exchange. Our data indicate that AAC is predominantly in the cytosol-facing open state and converts to a sparsely populated state in an asymmetric manner despite its three-fold structural symmetry. Binding of the substrate ADP substantially increases the rate of conformational exchange, whereas the inhibitor CATR slows the exchange. These results suggest that although the transporter catalyzes the translocation of substrate the substrate also facilitates interconversion between alternating states, and this interconversion may be relevant to the transport function.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Brüschweiler
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: 1] National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China. [2] State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Run
authors.affiliation: 1] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA. [2] National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China. [3] State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
authors.forename: James J
authors.initials: JJ
authors.lastname: Chou
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000465:Algorithms; D001665:Binding Sites; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D000244:Adenosine Diphosphate; D000226:Mitochondrial ADP, ATP Translocases