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Polymorphic A?42 fibrils adopt similar secondary structure but differ in cross-strand side chain stacking interactions within the same ?-sheet.


ABSTRACT: Formation of polymorphic amyloid fibrils is a common feature in neurodegenerative diseases involving protein aggregation. In Alzheimer's disease, different fibril structures may be associated with different clinical sub-types. Structural basis of fibril polymorphism is thus important for understanding the role of amyloid fibrils in the pathogenesis and progression of these diseases. Here we studied two types of A?42 fibrils prepared under quiescent and agitated conditions. Quiescent A?42 fibrils adopt a long and twisted morphology, while agitated fibrils are short and straight, forming large bundles via lateral association. EPR studies of these two types of A?42 fibrils show that the secondary structure is similar in both fibril polymorphs. At the same time, agitated A?42 fibrils show stronger interactions between spin labels across the full range of the A?42 sequence, suggesting a more tightly packed structure. Our data suggest that cross-strand side chain packing interactions within the same ?-sheet may play a critical role in the formation of polymorphic fibrils.

SUBMITTER: Wang H 

PROVIDER: S-EPMC7109039 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Polymorphic Aβ42 fibrils adopt similar secondary structure but differ in cross-strand side chain stacking interactions within the same β-sheet.

Wang Hongsu H   Duo Lan L   Hsu Frederick F   Xue Christine C   Lee Yoon Kyung YK   Guo Zhefeng Z  

Scientific reports 20200331 1


Formation of polymorphic amyloid fibrils is a common feature in neurodegenerative diseases involving protein aggregation. In Alzheimer's disease, different fibril structures may be associated with different clinical sub-types. Structural basis of fibril polymorphism is thus important for understanding the role of amyloid fibrils in the pathogenesis and progression of these diseases. Here we studied two types of Aβ42 fibrils prepared under quiescent and agitated conditions. Quiescent Aβ42 fibrils  ...[more]

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