Solution NMR studies of antiamoebin, a membrane channel-forming polypeptide.
Antiamoebin I is a membrane-active peptaibol produced by fungi of the species Emericellopsis which is capable of forming ion channels in membranes. Previous structure determinations by x-ray crystallography have shown the molecule is mostly helical, with a deep bend in the center of the polypeptide, and that the backbone structure is independent of the solvent used for crystallization. In this study, the solution structure of antiamoebin was determined by NMR spectroscopy in methanol, a solvent from which one of the crystal structures was determined. The ensemble of structures produced exhibit a right-handed helical C terminus and a left-handed helical conformation toward the N-terminus, in contrast to the completely right-handed helices found in the crystal structures. The NMR results also suggest that a "hinge" region exists, which gives flexibility to the polypeptide in the central region, and which could have functional implications for the membrane insertion process. A model for the membrane insertion and assembly process is proposed based on the antiamoebin solution and crystal structures, and is contrasted with the assembly and insertion mechanism proposed for other ion channel-forming polypeptides.
Galbraith
T P
TP
School of Crystallography, Birkbeck College, University of London, UK.
Harris
R
R
Driscoll
P C
PC
Wallace
B A
BA
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003198:Computer Simulation; D003461:Crystallography / Q000379:methods; D006860:Hydrogen Bonding; D007473:Ion Channels / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D054848:Peptaibols; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012996:Solutions / Q000737:chemistry
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D054848:Peptaibols; D010455:Peptides; D012996:Solutions; C006596:antiamoebin