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Structure of the Alamethicin Pore Reconstructed by X-Ray Diffraction Analysis

Shuo Qian ^*, Wangchen Wang ^*, Lin Yang  and Huey W. Huang ^*

^* Department of Physics and Astronomy, Rice University, Houston, Texas 77251; and National Synchrotron Light Source, Brookhaven National Laboratory, Upton, New York 11973

Correspondence: Address reprint request to Dr. Huey W. Huang, Dept. of Physics and Astronomy, Rice University, Houston, TX 77251-1892. Tel.: 713-3484899; Fax: 713-3484150; E-mail: hwhuang{at}rice.edu.

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 where pores were present, as established previously by neutron in-plane scattering in correlation with oriented circular dichroism. At dehydrated conditions, the interbilayer 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 performed multiwavelength anomalous diffraction at the bromine K edge. The result unambiguously shows that the alamethicin pore is of the barrel-stave type consisting of eight 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 at which alamethicin was tested for its antibacterial activity.