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Method of X-Ray Anomalous Diffraction for Lipid Structures

Wangchen Wang ^*, Deng Pan ^*, Yang Song ^*, Wenhan Liu ^*, Lin Yang  and Huey W. Huang ^*

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

Correspondence: Address reprint requests to Dr. Huey W. Huang, Dept. of Physics & Astronomy, Rice University, Houston, Texas 77251-1892. Tel.: 713-348-4899; Fax: 713-348-4150; E-mail: hwhuang{at}rice.edu.

The structures of the unit cells of lipid phases that exhibit long-range crystalline order but short-range liquid-like disorder are of biological interests. In particular, the recently discovered rhombohedral phase has a unit cell containing either the structure of a membrane fusion intermediate state or that of a peptide-induced transmembrane pore, depending on the lipid composition and participating peptides. Diffraction from such systems generally presents a difficult phase problem. The existing methods of phase determination all have their limitations. Therefore it is of general interest to develop a new phasing method. The method of multi-wavelength anomalous dispersion is routinely used in protein crystallography, but the same method is difficult for lipid systems for the practical reason that the commonly used lipid samples for diffraction do not have a well-defined thickness. Here we describe a practical approach to use the multi-wavelength anomalous dispersion method for lipid structures. The procedure is demonstrated with the lamellar phase of a brominated lipid. The method is general to all phases as long as anomalous diffraction is applicable.

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