title: Increasing the amphiphilicity of an amyloidogenic peptide changes the beta-sheet structure in the fibrils from antiparallel to parallel.
abstract: Solid-state NMR measurements have been reported for four peptides derived from beta-amyloid peptide Abeta(1-42): Abeta(1-40), Abeta(10-35), Abeta(16-22), and Abeta(34-42). Of these, the first two are predicted to be amphiphilic and were reported to form parallel beta-sheets, whereas the latter two peptides appear nonamphiphilic and adopt an antiparallel beta-sheet organization. These results suggest that amphiphilicity may be significant in determining fibril structure. Here, we demonstrate that acylation of Abeta(16-22) with octanoic acid increases its amphiphilicity and changes the organization of fibrillar beta-sheet from antiparallel to parallel. Electron microscopy, Congo Red binding, and one-dimensional 13C NMR measurements demonstrate that octanoyl-Abeta(16-22) forms typical amyloid fibrils. Based on the stability of monolayers at the air-water interface, octanoyl-Abeta(16-22) is more amphiphilic than Abeta(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-Abeta(16-22) fibrils are composed of parallel beta-sheets, whereas Abeta(16-22) fibrils are composed of antiparallel beta-sheets. These data demonstrate that amphiphilicity is critical in determining the structural organization of beta-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.
authors.affiliation: Department of Biochemistry, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gordon
authors.forename: John J
authors.initials: JJ
authors.lastname: Balbach
authors.forename: Robert
authors.initials: R
authors.lastname: Tycko
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Meredith
mesh_terms: D000215:Acylation; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure*; D002210:Caprylates / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010455:Peptides; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D002210:Caprylates; D010455:Peptides; D012996:Solutions; D014867:Water; C031492:octanoic acid