The structure and function of antiamoebin I, a proline-rich membrane-active polypeptide.
BACKGROUND
Antiamoebin is a member of the peptaibol family of polypeptides and has a unique antibiotic activity: it acts as an antiamoebic agent, but does not effectively haemolyze erythrocytes even though it does exhibit membrane-modifying activity.


RESULTS
The structure of antiamoebin I has been determined by X-ray crystallography at 1.4 A resolution. The molecule forms a helical structure, which, as a result of the presence of a number of proline and hydroxyproline residues, has a deep bend in the middle. Circular dichroism spectroscopy, single-channel conductance studies and fluorescence diffusion studies suggest a mode of ion transport that is entirely different from that of the other two members of the peptaibol family (alamethicin and zervamicin) whose structures and functions have been examined in detail.


CONCLUSIONS
The structure of the polypeptide has been determined and a functional model for its mode of action in membranes is presented. Although under some conditions antiamoebin may form ion channels, unlike the closely related alamethicin and zervamicin polypeptides, its major membrane-modifying activity appears to be as an ion carrier.
Snook
C F
CF
Department of Crystallography Birkbeck College University of London London, WC1E 7HX, UK.
Woolley
G A
GA
Oliva
G
G
Pattabhi
V
V
Wood
S F
SF
Blundell
T L
TL
Wallace
B A
BA
D000408:Alamethicin / Q000737:chemistry; D000563:Amebicides / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D008566:Membranes / Q000187:drug effects; D008956:Models, Chemical; D008958:Models, Molecular; D054848:Peptaibols; D010455:Peptides; D011392:Proline
D000563:Amebicides; D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D054848:Peptaibols; D010455:Peptides; C006596:antiamoebin; C069342:zervamicin Z-L; D000408:Alamethicin; D011392:Proline