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- Title
α-Synuclein exhibits competitive interaction between calmodulin and synthetic membranes.
- Authors
Lee, D.; Lee, S-Y.; Lee, E-N.; Chang, C-S.; Paik, S.R.
- Abstract
α-Synuclein, a pathological component of Parkinson's disease by constituting the Lewy bodies, has been suggested to be involved in membrane biogenesis via induction of amphipathic α-helices. Since the amphipathic α-helix is also known as a recognition signal of calmodulin for its target proteins, molecular interaction between α-synuclein and calmodulin has been investigated. By employing a chemical coupling reagent of N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline, α-synuclein has been shown to yield a heterodimeric 1 : 1 complex with calmodulin on sodium dodecyl sulfate–polyacrylamide gel electrophoresis in the presence and even absence of calcium, whereas β-synuclein was more dependent upon calcium for its calmodulin interaction. The selective calmodulin interaction of α-synuclein in the absence of calcium was also demonstrated with the aggregation kinetics of the synucleins in which only the α-synuclein aggregation was affected by calmodulin. A reversible binding assay confirmed that α-synuclein interacted with the Ca[sup 2+]-free as well as the Ca[sup 2+]-bound calmodulins with almost identical K[sub d]s of 0.35 µm and 0.31 µm, respectively, while β-synuclein preferentially recognized the Ca[sup 2+]-bound form with a K[sub d] of 0.68 µm. By using a C-terminally truncated α-synuclein of α-syn97, the calmodulin binding site(s) on α-synuclein was(were) shown to be located on the N-terminal region where the amphipathic α-helices have been suggested to be induced upon membrane interaction. By employing liposome and calmodulin in a state of being either soluble or immobilized on agarose, actual competition of α-synuclein between membranes and calmodulin was demonstrated with the observation that α-synuclein previously bound to the liposome was released upon specific interaction with the calmodulins. Taken together, these data may suggest that α-synuclein could act not only as a negative regulator for calmodulin in the presence and even absence of calcium, but it could also exert its activity at the interface between calmodulin and membranes.
- Subjects
PARKINSON'S disease; CALMODULIN
- Publication
Journal of Neurochemistry, 2002, Vol 82, Issue 5, p1007
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2002.01024.x