Biomedical subjects

Cynthia Paul

Publications and source records attributed to Cynthia Paul.

3 recordsLinked to original sources

PubMed2005

beta Sheet structure in amyloid beta fibrils and vibrational dipolar coupling.

Fibrils formed by amyloid beta proteins were labeled with 13C at various positions and examined by infrared spectroscopy to detect vibrational dipolar coupling, implying close physical proximity. The results support key features of several recently proposed models for amyloid fibril structure, but they also add some important caveats. For instance, they support the conclusion that the beta structure is parallel; however, the coupling is not as strong as expected when residues are in register. This may be explained by out-of-register alignment of adjacent strands, or nonstandard parallel sheet structure that yields suboptimal alignment of labeled dipole moments. The data also point to a significant structural difference between fibrils formed by the 40-residue amyloid beta protein and fibrils formed by residues 10-35.

Amyloid beta-Peptides↗

PubMed2004

Vibrational coupling, isotopic editing, and beta-sheet structure in a membrane-bound polypeptide.

The N-acetylated hexapeptide WLLLLL (AcWL5) partitions into lipid membranes and is believed to assemble into an antiparallel beta-sheet. As a test of this structural assignment, the peptide bonds of residues 2-6 were labeled with (13)C and allowed to adsorb onto a supported lipid membrane. Peptides bound to the membrane were examined for evidence of coupling between the labeled vibrational modes in adjacent beta-strands with internal reflection infrared spectroscopy. Experimental results indicate that the amide I absorption band in D(2)O (i.e., amide I') attributable to (13)C is selectively enhanced when the label is at any one of several positions along the peptide backbone. Simulations employing an excitonic model with through-bond and through-space interactions were performed on AcWL5 models in parallel and antiparallel beta-sheet configurations. The simulations yield spectra in good agreement with the experimental results, accounting for the enhancement of both (13)C band intensities and band frequencies. They also yield insight into the physical origin and structure selectivity of the distinctive amide I' band shapes that arise in isotopically edited spectra. It is concluded that the beta-sheet formed by membrane-bound AcWL5 is indeed antiparallel, and the enhancement of (13)C bands in the infrared spectra of these peptides is caused by both interstrand and intrastrand coupling to (12)C modes.

Amides↗

PubMed2003

Early synergy between Abeta42 and oxidatively damaged membranes in promoting amyloid fibril formation by Abeta40.

Oxidative lipid membrane damage is known to promote the misfolding of Abeta42 into pathological beta structure. In fully developed senile plaques of Alzheimer's disease, however, it is the shorter and more soluble amyloid beta protein, Abeta40, that predominates. To investigate the role of oxidative membrane damage in the misfolding of Abeta40, we have examined its interaction with supported lipid monolayer membranes using internal reflection infrared spectroscopy. Oxidatively damaged lipids modestly increased Abeta40 accumulation, with adsorption kinetics and a conformation that are distinct from that of Abeta42. In stark contrast, pretreatment of oxidatively damaged monolayer membranes with Abeta42 vigorously promoted Abeta40 accumulation and misfolding. Pretreatment of saturated or undamaged membranes with Abeta42 had no such effect. Parallel studies of lipid bilayer vesicles using a dye binding assay to detect fibril formation and electron microscopy to examine morphology demonstrated that Abeta42 pretreatment of oxidatively damaged membranes promoted the formation of mature Abeta40 amyloid fibrils. We conclude that oxidative membrane damage and Abeta42 act synergistically at an early stage to promote fibril formation by Abeta40. This synergy could be detected within minutes using internal reflection spectroscopy, whereas a dye-binding assay required several days and much higher protein concentrations to demonstrate this synergy.

Amyloid↗