Journal article
Increasing the Amphiphilicity of an Amyloidogenic Peptide Changes the β-Sheet Structure in the Fibrils from Antiparallel to Parallel
Biophysical journal, Vol.86(1), pp.428-434
01/2004
DOI: 10.1016/S0006-3495(04)74119-3
PMCID: PMC1303808
PMID: 14695285
Abstract
Solid-state NMR measurements have been reported for four peptides derived from
β
-amyloid peptide A
β
(1–42): A
β
(1–40), A
β
(10–35), A
β
(16–22), and A
β
(34–42). Of these, the first two are predicted to be amphiphilic and were reported to form parallel
β
-sheets, whereas the latter two peptides appear nonamphiphilic and adopt an antiparallel
β
-sheet organization. These results suggest that amphiphilicity may be significant in determining fibril structure. Here, we demonstrate that acylation of A
β
(16–22) with octanoic acid increases its amphiphilicity and changes the organization of fibrillar
β
-sheet from antiparallel to parallel. Electron microscopy, Congo Red binding, and one-dimensional
13
C NMR measurements demonstrate that octanoyl-A
β
(16–22) forms typical amyloid fibrils. Based on the stability of monolayers at the air-water interface, octanoyl-A
β
(16–22) is more amphiphilic than A
β
(16–22). Measurements of
13
C-
13
C and
15
N-
13
C 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-A
β
(16–22) fibrils are composed of parallel
β
-sheets, whereas A
β
(16–22) fibrils are composed of antiparallel
β
-sheets. These data demonstrate that amphiphilicity is critical in determining the structural organization of
β
-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.
Details
- Title: Subtitle
- Increasing the Amphiphilicity of an Amyloidogenic Peptide Changes the β-Sheet Structure in the Fibrils from Antiparallel to Parallel
- Creators
- David J Gordon - Departments of Biochemistry and Molecular Biology andJohn J Balbach - Departments of Biochemistry and Molecular Biology andRobert Tycko - Departments of Biochemistry and Molecular Biology andStephen C Meredith - Departments of Biochemistry and Molecular Biology and
- Resource Type
- Journal article
- Publication Details
- Biophysical journal, Vol.86(1), pp.428-434
- Publisher
- Biophysical Society
- DOI
- 10.1016/S0006-3495(04)74119-3
- PMID
- 14695285
- PMCID
- PMC1303808
- ISSN
- 0006-3495
- eISSN
- 1542-0086
- Language
- English
- Date published
- 01/2004
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984093316502771
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