title: Second transmembrane domain of human uncoupling protein 2 is essential for its anion channel formation.
abstract: Uncoupling proteins (UCP) are known to transport anions, such as Cl-, in addition to H+ transport. Although H+ transport by UCP is clearly involved in thermogenesis, the mechanism of its anion transport is not clearly understood. In this study, we examined the anion channel characteristics of the six individual helical transmembrane (TM) domains of the human UCP2. The second TM domain peptide (TM2) forms multi-state channels by assemblies of conductive oligomers. Furthermore, the TM2 exhibited voltage-dependent anion channels with properties comparable to those of UCP1 chloride channel. However, the other five TM peptides did not form UCP1-like channels. Moreover, an analog of TM2 in which two Arg residues were substituted by Ala residues did not form stable channels, implying the significance of Arg residues for anion transport. These results suggest that the anion channel structure of UCP2 protein is oligomeric and the second TM domain is essential for the voltage-dependence of this anion channel.
authors.affiliation: Department of Chemistry, Faculty of Science and Engineering, Saga University, 840-8502, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Masoud
authors.initials: M
authors.lastname: Jelokhani-Niaraki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kodama
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions; D001120:Arginine / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D007473:Ion Channels / Q000096:biosynthesis*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D000071246:Uncoupling Protein 2
chemical_list: D000838:Anions; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D001120:Arginine