Model for a Helical Bundle Channel Based on the High-Resolution Crystal Structure of Trichotoxin_A50E

• Published in: Biochemistry (Easton) Vol. 41; no. 43; pp. 12934 - 12941
• Main Authors: Chugh, J. K, Brückner, H, Wallace, B. A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 29.10.2002
• Subjects: Acetonitriles - chemistry; Anti-Bacterial Agents - chemistry; Computer Simulation; Crystallization; Crystallography, X-Ray; Hydrogen Bonding; Ion Channels - chemistry; Models, Molecular; Peptides; Protein Structure, Secondary; Sequence Alignment; Sequence Homology, Amino Acid; Software; Solvents; Water - chemistry
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi026150z

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 Å. 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° located between residues 10−13. Trichotoxin is the first solved structure of the peptaibol family that is all α-helix as opposed to containing part or all 310-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 ∼4−5 Å 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.