Beta-sheet templating of amyloid-beta protein by anionic phosphatidylglycerol membranes

COLL 72

Amy M. Winans, amyw@uchicago.edu1, Eva Y. Chi, evachi@fenjing.com2, Canay Ege, canayege@midway.uchicago.edu3, Jaroslaw Majewski, jarek@lanl.gov4, Kristian Kjaer, kristian.kjaer@nbi.ku.dk5, and Ka Yee C. Lee, kayeelee@uchicago.edu2. (1) Department of Chemistry, The Institute for Biophysical Dynamics and The James Franck Insitute, The University of Chicago, CIS-ESB31, 929 E. 57th Street, Chicago, IL 60637, (2) Department of Chemistry, The Institute for Biophysical Dynamics and The James Franck Institute, The University of Chicago, CIS-ESB31, 929 E. 57th Street, Chicago, IL 60637, (3) Department of Chemistry, The Insitute for Biophysical Dynamics and The James Franck Institute, The University of Chicago, CIS-ESB31, 929 E. 57th Street, Chicago, IL 60637, (4) LANSCE-12, Los Alamos National Laboratory, MS H805, Los Alamos, NM 87544, (5) Niels Bohr Institute, University of Copenhagen, DK-2100 Copenhagen, Denmark
Neuronal death leading to the dementia characteristic of Alzheimer's disease has been attributed to the misfolding and aggregation of the amyloid-beta protein, where normally-soluble amyloid-beta is found deposited in insoluble amyloid plaques rich in beta-sheet structure. A large body of research has implicated the cell membrane in this transition. We examined the interaction between charged and zwitterionic lipid monolayers and amyloid-beta on both pure water and buffered subphases using grazing incident x-ray diffraction and x-ray reflectivity. X-ray data revealed an ordering of amyloid-beta in water under a phosphatidylglycerol monolayer, with d-spacings that matched beta-sheet spacings found in amyloid fibrils. Amyloid-beta was then incubated with bilayer vesicles to examine the effect of the templated-beta-sheet structure on fibril formation. Size-exclusion chromatography and Thioflavin-T fluorescence were used to monitor amyloid-beta fibril formation. Our results show that phosphatidylglycerol promoted fibril formation in water, supporting the templating phenomenon seen in the monolayer experiments.
 

Biological Surface Chemistry
8:30 AM-11:50 AM, Monday, March 26, 2007 McCormick Place South -- Room S404A, Level 4, Oral

Division of Colloid & Surface Chemistry

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007