Structural highlights
FunctionPPIA_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Publication Abstract from PubMedPeptidylprolyl isomerases (PPIases) catalyze cis/trans isomerization of prolines. The PPIase CypA colocalizes with the Parkinson's disease (PD)-associated protein alpha-synuclein in cells and interacts with alpha-synuclein oligomers. Herein, we describe atomic insights into the molecular details of the alpha-synuclein/CypA interaction. NMR spectroscopy shows that CypA catalyzes isomerization of proline 128 in the C-terminal domain of alpha-synuclein. Strikingly, we reveal a second CypA-binding site formed by the hydrophobic sequence (47) GVVHGVATVA(56) , termed PreNAC. The 1.38 A crystal structure of the CypA/PreNAC complex displays a contact between alanine 53 of alpha-synuclein and glutamine 111 in the catalytic pocket of CypA. Mutation of alanine 53 to glutamate, as found in patients with early-onset PD, weakens the interaction of alpha-synuclein with CypA. Our study provides high-resolution insights into the structure of the PD-associated protein alpha-synuclein in complex with the most abundant cellular cyclophilin. The Molecular Basis of the Interaction of Cyclophilin A with alpha-Synuclein.,Favretto F, Baker JD, Strohaker T, Andreas LB, Blair LJ, Becker S, Zweckstetter M Angew Chem Int Ed Engl. 2019 Dec 12. doi: 10.1002/anie.201914878. PMID:31830361[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
This page was last modified 11:45, 24 January 2024.