Molecular Aspects of the Adenine Nucleotide Carrier from Mitochondria

  • M. Klingenberg


The primary structure of the ADP/ATP carrier (AAC), first established for the bovine heart carrier, showed a relatively wide distribution of hydrophilic residues which permits assignment of only two hydrophobic transmembrane stretches. However, a striking tripartition of the primary structure into three 100-residue long domains allows a more significant assignment of transmembrane elements. With proper alignment of these three domains for maximum conservation of structurally critical residues, each domain can be assigned to have two transmembrane α-elements which are in each case 18 and 22 residues long, respectively. The interdomain homology between these α-regions is low. The central regions flanked by these helices contain most of the polar residues and are significantly interdomain conserved. With lysine probes the central regions are assigned to the matrix side (m-side) and the two connecting regions as well as C- and N-terminal to the cytosolic side (c-side). Out of the central regions a loop is assumed to protrude through the membrane, probably for lining the translocation channel. This localization of a major protein mass within the membrane is in accordance with hydrodynamic evidence, the carrier being an oblate ellipsoid with only about 50 Å along the short axis. In accordance, the loops of domain 2 and 3 are affinity-labelled by azido-ADP or aryl-atractylate. Primary structures of AAC from other sources (fungi, plants) also exhibit the tripartition. The interdomain conserved residues are also interspecies conserved, thus showing that they are essential. These repeat domains have probably evolved from a common original gene of 100 residues length. Isoforms of the AAC exist, as shown by primary structure analysis of human cDNA libraries from different organs. Three different isoforms are identified in human organs. These isoforms may have developed in accordance with specific requirements of the various tissue metabolism on the ADP/ATP exchange.


Brown Adipose Tissue Human Skeletal Muscle Polar Residue Binding Center Beef Heart 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. Klingenberg
    • 1
  1. 1.Institut für Physikalische BiochemieUniversität MünchenMünchen 2Germany

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