National Institutes of Health/National Institute on Aging (NIH/NIA)
AG027317
米国
National Institutes of Health/National Institute on Aging (NIH/NIA)
AG061775
米国
引用
ジャーナル: J Struct Biol / 年: 2024 タイトル: An electrostatic cluster guides Aβ40 fibril formation in sporadic and Dutch-type cerebral amyloid angiopathy. 著者: Ziao Fu / Elliot J Crooks / Brandon A Irizarry / Xiaoyue Zhu / Saikat Chowdhury / William E Van Nostrand / Steven O Smith / 要旨: Cerebral amyloid angiopathy (CAA) is associated with the accumulation of fibrillar Aβ peptides upon and within the cerebral vasculature, which leads to loss of vascular integrity and contributes to ...Cerebral amyloid angiopathy (CAA) is associated with the accumulation of fibrillar Aβ peptides upon and within the cerebral vasculature, which leads to loss of vascular integrity and contributes to disease progression in Alzheimer's disease (AD). We investigate the structure of human-derived Aβ40 fibrils obtained from patients diagnosed with sporadic or familial Dutch-type (E22Q) CAA. Using cryo-EM, two primary structures are identified containing elements that have not been observed in in vitro Aβ40 fibril structures. One population has an ordered N-terminal fold comprised of two β-strands stabilized by electrostatic interactions involving D1, E22, D23 and K28. This charged cluster is disrupted in the second population, which exhibits a disordered N-terminus and is favored in fibrils derived from the familial Dutch-type CAA patient. These results illustrate differences between human-derived CAA and AD fibrils, and how familial CAA mutations can guide fibril formation.
全体 : Fibrillar assembly of human Amyloid-beta 1-40 derived from vascul...
全体
名称: Fibrillar assembly of human Amyloid-beta 1-40 derived from vascular deposits in a cerebral amyloid angiopathy patient
要素
複合体: Fibrillar assembly of human Amyloid-beta 1-40 derived from vascular deposits in a cerebral amyloid angiopathy patient
タンパク質・ペプチド: Amyloid-beta precursor protein
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超分子 #1: Fibrillar assembly of human Amyloid-beta 1-40 derived from vascul...
超分子
名称: Fibrillar assembly of human Amyloid-beta 1-40 derived from vascular deposits in a cerebral amyloid angiopathy patient タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all
由来(天然)
生物種: Homo sapiens (ヒト) / 器官: Brain / 組織: Vasculature