A structural model for apolipoprotein C-II amyloid fibrils : experimental characterization and molecular dynamics simulations

Teoh, C. L. and Pham, C. L. and Todorova, N. and Hung, A. and Lincoln, C. N. and Lees, E. and Lam, Y. H. and Binger, K. J. and Thomson, N. H. and Radford, S. E. and Smith, T. A. and Muller, S. A. and Engel, A. and Griffin, M. D. and Yarovsky, I. and Gooley, P. R. and Howlett, G. J.. (2011) A structural model for apolipoprotein C-II amyloid fibrils : experimental characterization and molecular dynamics simulations. Journal of molecular biology, Vol. 405, H. 5. pp. 1246-1266.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6002479

Downloads: Statistics Overview


The self-assembly of specific proteins to form insoluble amyloid fibrils is a characteristic feature of a number of age-related and debilitating diseases. Lipid-free human apolipoprotein C-II (apoC-II) forms characteristic amyloid fibrils and is one of several apolipoproteins that accumulate in amyloid deposits located within atherosclerotic plaques. X-ray diffraction analysis of aligned apoC-II fibrils indicated a simple cross-beta-structure composed of two parallel beta-sheets. Examination of apoC-II fibrils using transmission electron microscopy, scanning transmission electron microscopy, and atomic force microscopy indicated that the fibrils are flat ribbons composed of one apoC-II molecule per 4.7-A rise of the cross-beta-structure. Cross-linking results using single-cysteine substitution mutants are consistent with a parallel in-register structural model for apoC-II fibrils. Fluorescence resonance energy transfer analysis of apoC-II fibrils labeled with specific fluorophores provided distance constraints for selected donor-acceptor pairs located within the fibrils. These findings were used to develop a simple 'letter-G-like' beta-strand-loop-beta-strand model for apoC-II fibrils. Fully solvated all-atom molecular dynamics (MD) simulations showed that the model contained a stable cross-beta-core with a flexible connecting loop devoid of persistent secondary structure. The time course of the MD simulations revealed that charge clusters in the fibril rearrange to minimize the effects of same-charge interactions inherent in parallel in-register models. Our structural model for apoC-II fibrils suggests that apoC-II monomers fold and self-assemble to form a stable cross-beta-scaffold containing relatively unstructured connecting loops.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Engel)
UniBasel Contributors:Engel, Andreas H
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:14 Sep 2012 07:22
Deposited On:14 Sep 2012 07:15

Repository Staff Only: item control page