Interaction of alpha-synuclein and synphilin-1: effect of Parkinson's disease-associated mutations.

alpha-Synuclein is a major component of Lewy bodies, a neuropathological feature of Parkinson's disease. Two alpha-synuclein mutations, Ala53Thr and Ala30Pro, are associated with early onset, familial forms of the disease. Recently, synphilin-1, a protein found to interact with alpha-synuclein by yeast two hybrid techniques, was detected in Lewy bodies. In ...
this study we report the interaction of alpha-synuclein and synphilin-1 in human neuroglioma cells using a sensitive fluorescence resonance energy transfer technique. We demonstrate that the C-terminus of alpha-synuclein is closely associated with the C-terminus of synphilin-1. A weak interaction occurs between the N-terminus of alpha-synuclein and synphilin-1. The familial Parkinson's disease associated mutations of alpha-synuclein (Ala53Thr and Ala30Pro) also demonstrate a strong interaction between their C-terminal regions and synphilin-1. However, compared with wild-type alpha-synuclein, significantly less energy transfer occurs between the C-terminus of Ala53Thr alpha-synuclein and synphilin-1, suggesting that the Ala53Thr mutation alters the conformation of alpha-synuclein in relation to synphilin-1.
Mesh Terms:
Blotting, Western, Carrier Proteins, Energy Transfer, Fluorescent Antibody Technique, Indirect, Gene Expression, Glioma, Humans, Immunohistochemistry, Microscopy, Confocal, Mutagenesis, Site-Directed, Mutation, Nerve Tissue Proteins, Parkinson Disease, Protein Conformation, Structure-Activity Relationship, Subcellular Fractions, Synucleins, Transfection, Tumor Cells, Cultured, alpha-Synuclein
J. Neurochem.
Date: May. 01, 2001
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