Metal-assisted channel stabilization: disposition of a single histidine on the N-terminus of alamethicin yields channels with extraordinarily long lifetimes.
Alamethicin, a member of the peptaibol family of antibiotics, is a typical channel-forming peptide with a helical structure. The self-assembly of the peptide in the membranes yields voltage-dependent channels. In this study, three alamethicin analogs possessing a charged residue (His, Lys, or Glu) on their N-termini were designed with the expectation of stabilizing the transmembrane structure. A slight elongation of channel lifetime was observed for the Lys and Glu analogs. On the other hand, extensive stabilization of certain channel open states was observed for the His analog. This stabilization was predominantly observed in the presence of metal ions such as Zn(2+), suggesting that metal coordination with His facilitates the formation of a supramolecular assembly in the membranes. Channel stability was greatly diminished by acetylation of the N-terminal amino group, indicating that the N-terminal amino group also plays an important role in metal coordination.
Noshiro
Daisuke
D
Institute for Chemical Research, Kyoto University, Kyoto, Japan.
Asami
Koji
K
Futaki
Shiroh
S
D000408:Alamethicin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004553:Electric Conductivity; D005240:Feasibility Studies; D006639:Histidine; D007093:Imidazoles / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D055550:Protein Stability / Q000187:drug effects; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology
D007093:Imidazoles; D007473:Ion Channels; D008670:Metals; D010446:Peptide Fragments; D000408:Alamethicin; D006639:Histidine; C029899:imidazole; D015032:Zinc