Model for a helical bundle channel based on the high-resolution crystal structure of trichotoxin_A50E.
Trichotoxin_A50E is an 18-residue peptaibol antibiotic which forms multimeric transmembrane channels through self-association. The crystal structure of trichotoxin has been determined at a resolution of 0.9 A. The trichotoxin sequence contains nine helix-promoting Aib residues, which contribute to the formation of an entirely helical structure that has a central bend of 8-10 degrees located between residues 10-13. Trichotoxin is the first solved structure of the peptaibol family that is all alpha-helix as opposed to containing part or all 3(10)-helix. Gln residues in positions 6 and 17 produce a polar face, and are proposed to form the channel lumen. An octameric model channel has been constructed from the crystal structure. It has a central pore of approximately 4-5 A radius, a size sufficient to enable transport of ions, with a constricted region at one end, formed by a ring of Gln6 residues. Electrostatic calculations are consistent with it being a cationic channel.
Chugh
J K
JK
Department of Crystallography, Birkbeck College, University of London, London WC1E 7HX, UK.
Brückner
H
H
Wallace
B A
BA
D000097:Acetonitriles / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D003198:Computer Simulation; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007473:Ion Channels / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software; D012997:Solvents; D014867:Water / Q000737:chemistry
D000097:Acetonitriles; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D007473:Ion Channels; D010455:Peptides; D012997:Solvents; D014867:Water; C016161:trichotoxin; C032159:acetonitrile