Cyclophilin D binds to the acidic C-terminus region of alpha-Synuclein and affects its aggregation characteristics

Torpey, James, Madine, Jillian ORCID: 0000-0001-9963-5871, Wood, Amy and Lian, Lu-Yun
(2020) Cyclophilin D binds to the acidic C-terminus region of alpha-Synuclein and affects its aggregation characteristics. SCIENTIFIC REPORTS, 10 (1). 10159-.

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Cyclophilin D (CypD) is a peptidyl-prolyl isomerase expressed in the nucleus and transported into the mitochondria where it is best associated with the regulation of the mitochondrial permeability transition pore (MPTP). There are, however, other possible roles of CypD in the mitochondria which may or may not be linked with the MPTP. Alpha synuclein (αSyn) is shown here to interact directly with CypD via its acidic proline-rich C-terminus region and binding at the putative ligand binding pocket of CypD. The study shows that CypD binding with soluble αSyn prevents its aggregation. Furthermore, the addition of CypD to preformed αSyn fibrils leads to the disassembly of these fibrils. Enzymatically-compromised mutants of CypD show reduced abilities to dissociate αSyn aggregates, suggesting that fibril disassembly is linked to the increased rate of peptidyl-prolyl isomerisation catalysed by CypD. Protein aggregation in the mitochondria is increasingly seen as the cause of neurodegeneration. However, protein aggregation is a reversible process but disaggregation requires help from other proteins such as isomerases and chaperones. The results here demonstrate a possible mechanism by which CypD achieves this and suggest that disaggregation could be one of the many functions of this protein.

Item Type: Article
Uncontrolled Keywords: Mitochondria, Molecular Chaperones, Protein Binding, Catalysis, Solubility, alpha-Synuclein, In Vitro Techniques, Protein Aggregates, Protein Aggregation, Pathological, Mitochondrial Transmembrane Permeability-Driven Necrosis, Cyclohexane Monoterpenes, Cyclophilin D
Depositing User: Symplectic Admin
Date Deposited: 03 Jul 2020 10:24
Last Modified: 18 Jan 2023 23:47
DOI: 10.1038/s41598-020-66200-9
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