Crystal structure of the channel-forming polypeptide antiamoebin in a membrane-mimetic environment

^*Laboratory for the Structure of Matter, Naval Research Laboratory, Washington, DC 20375-5341; and ^‡Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India

Contributed by Isabella L. Karle

Abstract

Crystals of an ion-channel-forming peptaibol peptide in a partial membrane environment have been obtained by cocrystallizing antiamoebin with n-octanol. The antiamoebin molecule has a bent helical conformation very similar to that established for Leu-zervamicin, despite a significantly different sequence for residues 1–8. The bent helices assemble to form a polar channel in the shape of an hour glass that is quite comparable to that of Leu-zervamicin. The molecules of cocrystallized octanol are found in two different areas with respect to the assembly of peptide molecules. One octanol molecule mimics a membrane segment along the hydrophobic exterior of the channel assembly. The other octanol molecules fill the channel in such a way that their OH termini satisfy the C=O moieties directed into the interior of the channel. Structure parameters for C₈₂H₂₇N₁₇O₂₀⋅3C₈H₁₈O are space group P2₁2₁2₁, a = 9.143(2) Å, b = 28.590(8) Å, c = 44.289(8) Å, Z = 4, agreement factor R ₁ = 11.95% for 4,113 observed reflections [>4σ(F)], resolution ∼1.0 Å.

Footnotes

↵ † To whom reprint requests should be addressed at: Laboratory for the Structure of Matter, Code 6030, Naval Research Laboratory, Washington, DC 20375-5341.
Data deposition: The atomic coordinates have been deposited in the Cambridge Crystallographic Data Base, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, U.K. (accession no. CCDC 101253).
ABBREVIATIONS:

Aib,

α-aminoisobutyric acid;

Hyp,

4-hydroxyproline;

Iva,

isovaline (α-ethylalanine);

Phol,

phenylalaninol