Structural highlights
Publication Abstract from PubMed
Amyloid-beta (Abeta) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. Abeta molecules form beta-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of Abeta has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate Abeta polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of Abeta. These structures, all of short, self-complementing pairs of beta-sheets termed steric zippers, reveal a variety of modes of self-association of Abeta. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to Abeta. These structures and molecular models contribute fundamental information for understanding Abeta polymorphic nature and pathogenesis.
Molecular basis for amyloid-{beta} polymorphism.,Colletier JP, Laganowsky A, Landau M, Zhao M, Soriaga AB, Goldschmidt L, Flot D, Cascio D, Sawaya MR, Eisenberg D Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):16938-43. Epub 2011 Sep 23. PMID:21949245[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Colletier JP, Laganowsky A, Landau M, Zhao M, Soriaga AB, Goldschmidt L, Flot D, Cascio D, Sawaya MR, Eisenberg D. Molecular basis for amyloid-{beta} polymorphism. Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):16938-43. Epub 2011 Sep 23. PMID:21949245 doi:10.1073/pnas.1112600108
