3OW9

Structure of an amyloid forming peptide KLVFFA from amyloid beta, alternate polymorph II

Summary for 3OW9

• Entry DOI: 10.2210/pdb3ow9/pdb
• Related: 3OVJ
• Descriptor: KLVFFA hexapeptide segment from Amyloid beta (2 entities in total)
• Functional Keywords: amyloid-like protofibril, protein fibril
• Cellular location: Membrane; Single-pass type I membrane protein: P05067
• Total number of polymer chains: 2
• Total formula weight: 1449.82

Authors

Landau, M.,Eisenberg, D. (deposition date: 2010-09-17, release date: 2011-08-31, Last modification date: 2024-02-21)

Primary citation

Colletier, J.P.,Laganowsky, A.,Landau, M.,Zhao, M.,Soriaga, A.B.,Goldschmidt, L.,Flot, D.,Cascio, D.,Sawaya, M.R.,Eisenberg, D.
Molecular basis for amyloid-{beta} polymorphism.
Proc.Natl.Acad.Sci.USA, 108:16938-16943, 2011

PubMed Abstract: Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. Aβ molecules form β-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 Aβ has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate Aβ polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of Aβ. These structures, all of short, self-complementing pairs of β-sheets termed steric zippers, reveal a variety of modes of self-association of Aβ. 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 Aβ. These structures and molecular models contribute fundamental information for understanding Aβ polymorphic nature and pathogenesis.

PubMed: 21949245
DOI: 10.1073/pnas.1112600108

Experimental method

X-RAY DIFFRACTION (1.8 Å)