The uncoupling protein from brown fat mitochondria is related to the mitochondrial ADP/ATP carrier. Analysis of sequence homologies and of folding of the protein in the membrane.
We report here, for the first time, the primary structure of uncoupling protein as established by amino acid sequencing. Like the ADP/ATP carrier, this protein has a tripartite structure comprising three similar sequences of approximately 100 residues each. These six 'repeats' exhibit striking conservation of several residues, in particular glycine and proline, at possible structurally strategic positions. Although the two proteins differ strongly in their amino acid composition, their sequences are distantly homologous. Three membrane-spanning alpha-helices can be deduced from hydropathy plots. A modified plot accounting for amphiphilic helices indicates 5-6 such alpha-segments. In addition an amphiphilic beta-strand of membrane-spanning length can be discerned. The tripartite sequence structure is also distinctly reflected in the hydropathy distribution. Based on the membrane disposition of the segments of the ADP/ATP carrier, a model for the transmembrane folding path of the polypeptide chain of the uncoupling protein is proposed.
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D002417:Cattle; D003488:Cyanogen Bromide; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics*; D024101:Mitochondrial Proteins; D009713:Nucleotidyltransferases / Q000235:genetics*; D010446:Peptide Fragments / Q000032:analysis; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010446:Peptide Fragments; D000071256:Uncoupling Protein 1; D000226:Mitochondrial ADP, ATP Translocases; D009713:Nucleotidyltransferases; D003488:Cyanogen Bromide