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Biophysical Journal 86:428-434 (2004)
© 2004 The Biophysical Society

Increasing the Amphiphilicity of an Amyloidogenic Peptide Changes the ß-Sheet Structure in the Fibrils from Antiparallel to Parallel

David J. Gordon *, John J. Balbach {ddagger}, Robert Tycko {ddagger} and Stephen C. Meredith * {dagger}

* Departments of Biochemistry and Molecular Biology and {dagger} Pathology, The University of Chicago, Chicago, Illinois 60637; and {ddagger} Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520

Correspondence: Address reprint requests to Stephen C. Meredith, Dept. of Pathology, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637. Tel.: 773-702-1267; Fax: 773-834-5251; E-mail: scmeredi{at}midway.uchicago.edu.

Solid-state NMR measurements have been reported for four peptides derived from ß-amyloid peptide Aß(1–42): Aß(1–40), Aß(10–35), Aß(16–22), and Aß(34–42). Of these, the first two are predicted to be amphiphilic and were reported to form parallel ß-sheets, whereas the latter two peptides appear nonamphiphilic and adopt an antiparallel ß-sheet organization. These results suggest that amphiphilicity may be significant in determining fibril structure. Here, we demonstrate that acylation of Aß(16–22) with octanoic acid increases its amphiphilicity and changes the organization of fibrillar ß-sheet from antiparallel to parallel. Electron microscopy, Congo Red binding, and one-dimensional 13C NMR measurements demonstrate that octanoyl-Aß(16–22) forms typical amyloid fibrils. Based on the stability of monolayers at the air-water interface, octanoyl-Aß(16–22) is more amphiphilic than Aß(16–22). Measurements of 13C-13C and 15N-13C nuclear magnetic dipole-dipole couplings in isotopically labeled fibril samples, using the constant-time finite-pulse radiofrequency-driven recoupling (fpRFDR-CT) and rotational echo double resonance (REDOR) solid-state NMR techniques, demonstrate that octanoyl-Aß(16–22) fibrils are composed of parallel ß-sheets, whereas Aß(16–22) fibrils are composed of antiparallel ß-sheets. These data demonstrate that amphiphilicity is critical in determining the structural organization of ß-sheets in the amyloid fibril. This work also shows that all amyloid fibrils do not share a common supramolecular structure, and suggests a method for controlling the structure of amyloid fibrils.




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