Molecular modeling of the core of Abeta amyloid fibrils.
Amyloid fibrils, a key pathological feature of Alzheimer's disease (AD) and other amyloidosis implicated in neurodegeneration, have a characteristic cross-beta structure. Here we present a structural model for the core of amyloid fibrils formed by the Abeta peptide using computational approaches and experimental data. Abeta(15-36) was threaded against the parallel beta-helical proteins. Our multi-layer model was constructed using the top scoring template 1lxa, a left-handed parallel beta-helical protein. This six-rung helical model has in-register repeats of the Abeta(15-36) sequence. Each rung has three beta-strands separated by two turns. The model was tested using molecular dynamics simulations in explicit water, and is in good agreement with a number of experimental observations. In addition, a model based on right-handed helical proteins is also described. The core structural model described here might serve as the building block of the Abeta(1-40) amyloid fibril as well as some other amyloid fibrils.
Guo
Jun-tao
JT
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA.
Wetzel
Ronald
R
Xu
Ying
Y
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D008958:Models, Molecular
D016229:Amyloid beta-Peptides