The properties of ion channels formed by zervamicins.
The zervamicins (Zrv) are a family of 16 residue peptaibol channel formers, related to the 20 residue peptaibol alamethicin (Alm), but containing a higher proportion of polar sidechains. Zrv-IIB forms multi-level channels in planar lipid (diphytanoyl phosphatidylcholine) bilayers in response to cis positive voltages. Analysis of the voltage and concentration dependence of macroscopic conductances induced by Zrv-IIB suggests that, on average, channels contain ca. 13 peptide monomers. Analysis of single channel conductance levels suggests a similar value. The pattern of successive conductance levels is consistent with a modified helix bundle model in which the higher order bundle are distorted within the plane of the bilayer towards a "torpedo" shaped cross-section. The kinetics of intra-burst switching between adjacent conductance levels are shown to be approximately an order of magnitude faster for Zrv-IIB than for Alm. The channel forming properties of the related naturally occurring peptaibols, Zrv-Leu and Zrv-IC, have also been demonstrated, as have those of the synthetic apolar analogue Zrv-Al-16. The experimental studies on channel formation are combined with the known crystallographic structures of Zrv-Al-16 and Zrv-Leu to develop a molecular model of Zrv-IIB channels.
Balaram
P
P
Molecular Biophysics Unit, Indian Institute of Science, Bangalore.
Krishna
K
K
Sukumar
M
M
Mellor
I R
IR
Sansom
M S
MS
D000408:Alamethicin / Q000737:chemistry; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry; D055592:Biophysical Phenomena; D001703:Biophysics; D004553:Electric Conductivity; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008564:Membrane Potentials; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054848:Peptaibols; D010455:Peptides / Q000737:chemistry
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D054848:Peptaibols; D010455:Peptides; C074137:zervamicin A1-16; C069342:zervamicin Z-L; D000408:Alamethicin; C077076:zervamicin-IC; C077077:zervamicin IIB