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-Structure paper
タイトル | An electrostatic cluster guides Aβ40 fibril formation in sporadic and Dutch-type cerebral amyloid angiopathy. |
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ジャーナル・号・ページ | J Struct Biol, Vol. 216, Issue 2, Page 108092, Year 2024 |
掲載日 | 2024年4月13日 |
![]() | Ziao Fu / Elliot J Crooks / Brandon A Irizarry / Xiaoyue Zhu / Saikat Chowdhury / William E Van Nostrand / Steven O Smith / ![]() ![]() |
PubMed 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. |
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手法 | EM (らせん対称) |
解像度 | 2.87 - 7.77 Å |
構造データ | EMDB-29036, PDB-8ff2: EMDB-29037, PDB-8ff3: ![]() EMDB-29038: Amyloid-beta (1-40) fibrils derived from familial Dutch-type CAA patient (population A) |
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![]() | PROTEIN FIBRIL / amyloid / vascular / fibril / human |