ADP/ATP carrier protein

Beyer, K., KUngenberg, M., 1985, ADP/ATP carrier protein from beef heart mitochondria has high amounts oftightly bound cardioUpin, as revealed by P nuclear magnetic resonance. Biochemistry 24 3821-3826. 

An unusual glycoside, wedeloside (96), from Wedelia asperrima (Asteraceae), inhibits mitochondrial ADP/ATP carrier protein and has the ability to protect animals against the toxic effects of aflatoxin Bi (Croteau and Johnson, 1985 Node et al., 1982). Uie diterpene forskolin (97), from Coleus barbatus and C. forskohlii (Lamiaceae), is an activator of adenylate cyclase, and is an active inhibitor of the action of brefeldin A (a fungal metabolite with pronounced effects on protein trafficking in cells) (De Sousa and Shah, 1988 Schreiber, 1992 Valdes et al., 1987 Wagner, 1988). This compound also is of interest as an antihypertensive agent (Alcaraz and Rios, 1991 Hanson, 1991). 

Azidoacridine was used as photoaffinity label for nueleotide- and aromaticbinding sites in proteins [56,57]. The photochemistry of this azide was discussed in detail above. A radiolabeled [ H]7-azido-4-isopropylacridone upon irradiation specifically labeled (boimd covalently to) Cysl59 of the bovine mitochondrial ADP/ATP-carrier protein [103]. 

W. Oettmeier, K. Masson, S. Kalinna, [ H]7-Azido-4-isopropylacridone labels Cysl59 of the bovine mitochondrial ADP/ATP-carrier protein, Eur. J. Biochem., 1995, 227, 730-733. 

Many different data, which will be discussed below, are consistent with a mitochondrial origin of the hydrogenosomes of anaerobic chytrids their morphology, the mitochondrial-type targeting signals that are used to import proteins, the ADP/ATP carriers and mitochondrial-type chaperones, and all this supplemented by genomic analyses of separate hydrogenosomal proteins. 

The uncoupling protein is affected by several control mechanisms. It is inhibited by nucleotides such as GDP, GTP, ADP, and ATP which may bind at a site corresponding to that occupied by ATP or ADP in the ADP/ATP carrier.1 Uncoupling is stimulated by noradrenaline/ which causes a rapid increase in heat production by brown fat tissues, apparently via activation of adenylate cyclase. Uncoupling is also stimulated by fatty acids.) Recently UCP1 and related uncoupling proteins have been found to require both fatty acids and ubiquinone for activity.)) )k... 

This view amounts to mitochondrial genes being stuck where they are because of an insuperable difficulty if translocating hydrophobic proteins between subcelluar compartments. Yet there seems to be no evidence that hydrophobicity presents a particular barrier to protein import. For example, mitochondrial ADP-ATP carriers (AACs) are intrinsic to the mitochondrial inner membrane, have six transmembrane helices, and yet are encoded in the nucleus (Saraste and Walker 1982 van der Giezen et al. 2002). 

F. 10.12. Active transport by Na, K -ATPase. Three sodium ions bind to the transporter protein on the cytoplasmic side of the membrane. When ATP is hydrolyzed to ADP, the carrier protein is phosphorylated and undergoes a change in conformation that causes the sodium ions to be released into the extracellular fluid. Two potassium ions then bind on the extracellular side. Dephosphorylation of the carrier protein produces another conformational change, and the potassium ions are released on the inside of the cell membrane. The transporter protein then resumes its original conformation, ready to bind more sodium ions. 

The latest advance in the study of membrane protein by HX-MS was published by our group [16]. Following our previous study of the mitochondrial ADP/ATP carrier in detergent, a novel approach was proposed where the deuteration step is done in organello, on isolated mitochondria. This is the first HX-MS study of an integral membrane protein in its natural environment with all its possible... 

In the bovine heart mitochondrial ADP/ATP carrier, there are four cysteine residues Cys , Cys , Cys and Cys which are all at intervals of about 100 amino acid residues except Cys . This paper deals with the molecular mechanism of substrate transport by the carrier, deduced mainly from the effects of chemical modifications of its cysteine residues by SH-reagents under various conditions. The important role of the loops of the carrier in its transport function is described. Unless otherwise noted, the results were obtained with bovine heart submito-chondrial particles, in which the orientation of membrane proteins is inside-out relative to that of mitochondria. 

Fig. 2 Time courses of labelings by NEM and EMA of the four cysteine residue of the ADP/ATP carrier in bovine heart submitochondrial particles at 0 °C. Submitochondrial particles (20 mg protein/ml) were treated with EMA (20 nmols/mg protein) or NEM (100 nmols/mg protein) for various periods...

Klingenberg M. Dialectics in carrier research the ADP/ATP carrier and the uncoupling protein. J. Bioenerg. Biomembr. 1993 25 447-457. 

---