Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration.
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ABSTRACT:
SUBMITTER: Lv G
PROVIDER: S-EPMC11291021 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
Publications
Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration.
Lv Guohua G Sayles Nicole M NM Huang Yun Y Mancinelli Chiara D CD McAvoy Kevin K Shneider Neil A NA Manfredi Giovanni G Kawamata Hibiki H Eliezer David D
bioRxiv : the preprint server for biology 20240722
CHCHD10 is mutated in rare cases of FTD and ALS and aggregates in mouse models of disease. Here we show that the disordered N-terminal domain of CHCHD10 forms amyloid fibrils and report their cryoEM structure. Disease-associated mutations cannot be accommodated by the WT fibril structure, while sequence differences between CHCHD10 and CHCHD2 are tolerated, explaining the co-aggregation of the two proteins and linking CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration. ...[more]
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