Structural highlights
Publication Abstract from PubMedAlzheimer's disease is a progressive neurodegenerative disorder associated with the presence of amyloid-beta (Abeta) peptide fibrillar plaques in the brain. However, current evidence suggests that soluble nonfibrillar Abeta oligomers may be the major drivers of Abeta-mediated synaptic dysfunction. Structural information on these Abeta species has been very limited because of their noncrystalline and unstable nature. Here, we describe a crystal structure of amylogenic residues 18-41 of the Abeta peptide (equivalent to the p3 alpha/gamma-secretase fragment of amyloid precursor protein) presented within the CDR3 loop region of a shark Ig new antigen receptor (IgNAR) single variable domain antibody. The predominant oligomeric species is a tightly associated Abeta dimer, with paired dimers forming a tetramer in the crystal caged within four IgNAR domains, preventing uncontrolled amyloid formation. Our structure correlates with independently observed features of small nonfibrillar Abeta oligomers and reveals conserved elements consistent with residues and motifs predicted as critical in Abeta folding and oligomerization, thus potentially providing a model system for nonfibrillar oligomer formation in Alzheimer's disease. Crystal Structure of the Amyloid-{beta} p3 Fragment Provides a Model for Oligomer Formation in Alzheimer's Disease.,Streltsov VA, Varghese JN, Masters CL, Nuttall SD J Neurosci. 2011 Jan 26;31(4):1419-26. PMID:21273426[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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