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Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration
Guohua Lv1, Nicole M Sayles2, Yun Huang3,4
1Department of Biochemistry, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10021, United States.
None:
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.
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