Structure determination of micelle-like intermediates in amyloid beta -protein fibril assembly by using small angle neutron scattering.
Increasing evidence supports the hypothesis that amyloid beta-protein (Abeta) assembly is a key pathogenic feature of Alzheimer's disease. Thus, understanding the assembly process offers opportunities for the development of strategies for treating this devastating disease. In prior studies, Abeta was found to form micelle-like aggregates under acidic conditions. These structures exhibited an average observed hydrodynamic radius of 7 nm. They were found to be in rapid equilibrium with Abeta monomers or low molecular weight oligomers, and were centers of fibril nucleation. Here the technique of small angle neutron scattering has been used to determine the structure of these Abeta micelles. The data reveal that the micellar assemblies comprise 30-50 Abeta monomers and have elongated geometries. The best fit of the data to a uniform spherocylinder yields a radius approximately 2.4 nm and cylinder length approximately 11 nm. These structure parameters remain constant over more than a decade in concentration range. The concentration independence of the length of the cylindrical aggregate indicates the presence of an internal nonrepetitive structure that spans the entire length of the Abeta assembly.
Yong
Winnie
W
Department of Physics, Center for Materials Science and Engineering, and Materials Processing Center, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA.
Lomakin
Aleksey
A
Kirkitadze
Marina D
MD
Teplow
David B
DB
Chen
Sow-Hsin
SH
Benedek
George B
GB
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D055592:Biophysical Phenomena; D001703:Biophysics; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D008027:Light; D008823:Micelles; D009502:Neutrons; D010452:Peptide Biosynthesis; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D012542:Scattering, Radiation; D013997:Time Factors; D014867:Water / Q000737:chemistry
D016229:Amyloid beta-Peptides; D008823:Micelles; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D014867:Water