Home The mechanism of transport by mitochondrial carriers based on analysis of symmetry.
The mechanism of transport by mitochondrial carriers based on analysis of symmetry.
Title The mechanism of transport by mitochondrial carriers based on analysis of symmetry.
Authors Robinson, AJ, Overy, C, Kunji, ERS
Journal Proc Natl Acad Sci U S A
Keywords Amino Acid Sequence, Binding Sites, Humans, Mitochondrial ADP, ATP Translocases, Molecular Sequence Data, Protein Structure, Secondary, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
The structures of mitochondrial transporters and uncoupling proteins are 3-fold pseudosymmetrical, but their substrates and coupling ions are not. Thus, deviations from symmetry are to be expected in the substrate and ion-binding sites in the central aqueous cavity. By analyzing the 3-fold pseudosymmetrical repeats from which their sequences are made, conserved asymmetric residues were found to cluster in a region of the central cavity identified previously as the common substrate-binding site. Conserved symmetrical residues required for the transport mechanism were found at the water-membrane interfaces, and they include the three PX[DE]XX[RK] motifs, which form a salt bridge network on the matrix side of the cavity when the substrate-binding site is open to the mitochondrial intermembrane space. Symmetrical residues in three [FY][DE]XX[RK] motifs are on the cytoplasmic side of the cavity and could form a salt bridge network when the substrate-binding site is accessible from the mitochondrial matrix. It is proposed that the opening and closing of the carrier may be coupled to the disruption and formation of the 2 salt bridge networks via a 3-fold rotary twist induced by substrate binding. The interaction energies of the networks allow members of the transporter family to be classified as strict exchangers or uniporters.
DOI 10.1073/pnas.0809580105
Alternate Journal Proc. Natl. Acad. Sci. U.S.A.
Citation Key 10.1073/pnas.0809580105
MC_U105674181 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom