title: Conformation of the transmembrane domains in peripheral myelin protein 22. Part 1. Solution-phase synthesis and circular dichroism study of protected 17-residue partial peptides in the first putative transmembrane domain.
abstract: Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. DNA duplication and point mutation of the gene encoding peripheral myelin protein 22 (PMP22) have been found in CMT type 1A dominants. To investigate the influence of the point mutation of PMP22 on the secondary structure, protected partial peptides in the putative first transmembrane domain, wild type Boc-IVLH(Bom)VAVLVLLFVSTIV-OMe (1) and its Pro16 mutant Boc-IVLH(Bom)VAVPVLLFVSTIV-OMe (2) were synthesized. Circular dichorism (CD)-spectral analysis suggested that peptide 1 adopts a stable alpha-helical conformation in membrane-mimetic solvent,1-BuOH/1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) system. On the contrary, the mutant 2 favors beta-sheet conformation in the same solvent system. Interestingly, alpha-helix to beta-sheet transition of 2 was observed at higher contents of 1-BuOH than 70%.
authors.affiliation: Department of Chemistry, Gunma University, Gunma 376-8515, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: J
authors.initials: J
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Oku
authors.forename: R
authors.initials: R
authors.lastname: Katakai
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000138:chemical synthesis* / Q000737:chemistry*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D017354:Point Mutation; D011392:Proline / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D008565:Membrane Proteins; D009185:Myelin Proteins; C073687:PMP22 protein, human; D010446:Peptide Fragments; D011392:Proline