2Y29

Structure of segment KLVFFA from the amyloid-beta peptide (Ab, residues 16-21), alternate polymorph III

Summary for 2Y29

• Entry DOI: 10.2210/pdb2y29/pdb
• Related: 1AAP 1AMB 1AMC 1AML 1BA4 1BA6 1BJB 1BJC 1BRC 1CA0 1HZ3 1IYT 1MWP 1OWT 1QCM 1QWP 1QXC 1QYT 1RW6 1TAW 1TKN 1UO7 1UO8 1UOA 1UOI 1X11 1ZE7 1ZE9 1ZJD 2BEG 2BOM 2BP4 2WK3 2Y2A 2Y3J 2Y3K 2Y3L
• Descriptor: AMYLOID BETA A4 PROTEIN (2 entities in total)
• Functional Keywords: protein fibril, alzheimer disease
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Membrane; Single-pass type I membrane protein: P05067
• Total number of polymer chains: 1
• Total formula weight: 724.91

Authors

Colletier, J.,Laganowsky, A.,Sawaya, M.R.,Eisenberg, D. (deposition date: 2010-12-14, release date: 2011-10-26, Last modification date: 2024-05-08)

Primary citation

Colletier, J.,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-, 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 (2.3 Å)