Structure of the Alamethicin Pore
Reconstructed by X-ray Diffraction Analysis
Shuo Qian 1, Wangchen Wang 1, Lin Yang 2 and Huey W. Huang 1*
1 Rice University
2 Brookhaven National Laboratory
* To whom correspondence should be addressed. E-mail: hwhuang{at}rice.edu.
Submitted on November 25, 2007
Revised on December 9, 2007
Accepted on 14 December 2007
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Abstract |
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We reconstructed the electron density profile of the alamethicin-induced transmembrane pore by x-ray diffraction. We prepared fully hydrated multiple bilayers of alamethicin-lipid mixtures in a condition pores were present as established previously by neutron in-plane scattering in correlation with oriented circular dichroism. At dehydrated conditions the inter-bilayer distance shortened and the interactions between bilayers caused the membrane pores to become long-ranged correlated and form a periodically ordered lattice of rhombohedral symmetry. To resolve the phase problem of diffraction, we used a brominated lipid and perform multiwavelength anomalous diffraction at the bromine K edge. The result unambiguously shows that the alamethicin pore is of the barrel-stave type consisting of 8 alamethicin helices. This pore structure corresponds to the stable pores detected by neutron in-plane scattering in fully hydrated fluid bilayers at high peptide-lipid ratios, which are the conditions alamethicin was tested for its antibacterial activity.
Key Words:
Transmembrane pore, anomalous diffraction, antimicrobial peptides, barrel-stave model, peptide-induced pore, phase problem
