X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-. beta. conformation

Journal Article · Wed Jan 01 00:00:00 EST 1986 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.83.2.503· OSTI ID:6219314

Kirschner, D A; Abraham, C; Selkoe, D J

Information about the structure of the paired helical filaments (PHF) that accumulate within human neurons and the amyloid fibers that accumulate in the extracellular spaces between neurons in Alzheimer disease has so far depended on electron microscopy of thin-sectioned or negatively stained material. To determine the protein conformation of these abnormal fibers, the authors have obtained x-ray diffraction patterns from unfixed human brain fractions highly enriched in PHF and from purified amyloid cores isolated from senile plaques. The predominant x-ray scatter evident from both types of samples, either wet or dry, is a sharp reflection at 4.76-A spacing and a diffuse one at about 10.6-A spacing. These features are characteristic of a ..beta..-pleated sheet type of protein conformation. In doubly oriented dried pellets of PHF fractions, the two reflections are accentuated at right angles to each other and the arc at 4.76-A spacing is in the fiber direction indicating a cross-..beta.. conformation. From the integral widths of the reflections they estimate the cross-..beta.. crystallite to be about 80 A long in the fiber direction and about 40 A thick. These dimensions correspond to approximately four pleated sheets, each of which consists of approximately 16 hydrogen-bonded polypeptide chains running normal to the fiber direction. The cross-..beta.. conformation of PHF and amyloid fibers that they have found from x-ray diffraction in is contrast to the predominant ..cap alpha..-helical coiled-coil conformation of the neurofilaments with which they share epitopes and from which they have been postulated to derive.

• Research Organization: Harvard Medical School, Boston, MA (United States)
• OSTI ID: 6219314
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 83:2
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CELL CONSTITUENTS
PROTEIN STRUCTURE
NERVE CELLS
X-RAY DIFFRACTION
BRAIN
MAN
METABOLIC DISEASES
PATHOGENESIS
PROTEINS
PURIFICATION
ANIMAL CELLS
ANIMALS
BODY
CENTRAL NERVOUS SYSTEM
COHERENT SCATTERING
DIFFRACTION
DISEASES
MAMMALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PRIMATES
SCATTERING
SOMATIC CELLS
VERTEBRATES
550602* - Medicine- External Radiation in Diagnostics- (1980-)