3MOQ

Amyloid beta(18-41) peptide fusion with new antigen receptor variable domain from sharks

3MOQ の概要

• エントリーDOI: 10.2210/pdb3moq/pdb
• 分子名称: New antigen receptor variable domain,P3(40) peptide from Amyloid beta A4 protein,New antigen receptor variable domain (2 entities in total)
• 機能のキーワード: ab-ignar, ab-12y-2, receptor, amyloid, glycoprotein, membrane, protease inhibitor, serine protease inhibitor, transmembrane, amyloid beta fusion with ignar, chimera of immune system and amyloid peptide, immune system, neuropeptide
• 由来する生物種: Orectolobus maculatus (spotted wobbegong); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 53864.52

構造登録者

Streltsov, V.A. (登録日: 2010-04-23, 公開日: 2011-02-16, 最終更新日: 2024-10-30)

主引用文献

Streltsov, V.A.,Varghese, J.N.,Masters, C.L.,Nuttall, S.D.
Crystal Structure of the Amyloid-{beta} p3 Fragment Provides a Model for Oligomer Formation in Alzheimer's Disease
J.Neurosci., 31:1419-1426, 2011

PubMed Abstract: Alzheimer's disease is a progressive neurodegenerative disorder associated with the presence of amyloid-β (Aβ) peptide fibrillar plaques in the brain. However, current evidence suggests that soluble nonfibrillar Aβ oligomers may be the major drivers of Aβ-mediated synaptic dysfunction. Structural information on these Aβ 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 Aβ peptide (equivalent to the p3 α/γ-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 Aβ 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 Aβ oligomers and reveals conserved elements consistent with residues and motifs predicted as critical in Aβ folding and oligomerization, thus potentially providing a model system for nonfibrillar oligomer formation in Alzheimer's disease.

PubMed: 21273426
DOI: 10.1523/JNEUROSCI.4259-10.2011

実験手法

X-RAY DIFFRACTION (2.054 Å)