Novel inter- and intrasubunit contacts between transport-relevant residues of the homodimeric mitochondrial phosphate transport protein.
Ser158 is located near the middle of the matrix loop connecting transmembrane helices C and D of the mitochondrial phosphate transport protein (PTP). The mutant Ser158Thr PTP is transport-inactive. His32 is located near the middle of transmembrane helix A and Thr79 is located 5 residues away from transmembrane helix B and its N-terminal (matrix end). Single site mutant PTPs that have either residue replaced with Ala are transport-inactive. Based on the high resolution structure of a subunit of the bovine ADP/ATP translocase, on sequence similarities between members of the mitochondrial transport protein family, and on the PTP subunit/subunit contact site between transmembrane A helices, it is now suggested that the Ser158 site is at the PTP subunit/subunit contact site. This contact site is essential for keeping the transport cycles catalyzed by the two PTP subunits 180 degrees out of phase. The data also suggest that His32 and Thr79 of the same subunit interact and couple the phosphate and the proton transport paths.
Wohlrab
Hartmut
H
Boston Biomedical Research Institute, Department of Biological Chemistry and Molecular Pharmacology, and Harvard Medical School, Watertown, MA 02472, USA. wohlrab@bbri.org
D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D019281:Dimerization; D024101:Mitochondrial Proteins / Q000032:analysis / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D028061:Phosphate Transport Proteins / Q000032:analysis / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry*; D013329:Structure-Activity Relationship
D024101:Mitochondrial Proteins; D028061:Phosphate Transport Proteins; C422067:SLC25A3 protein, human; D012694:Serine