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Lookup NU author(s): Professor Tiago OuteiroORCiD
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© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.Proteins are structurally dynamic molecules that perform specialized functions through unique conformational changes accessible in physiological environments. An ability to specifically and selectively control protein function via conformational modulation is an important goal for development of novel therapeutics and studies of protein mechanism in biological networks and disease. Here we applied a second-harmonic generation-based technique for studying protein conformation in solution and in real time to the intrinsically disordered, Parkinson disease related protein α-synuclein. From a fragment library, we identified small molecule modulators that bind to monomeric α-synuclein in vitro and significantly reduce α-synuclein aggregation in a neuronal cell culture model. Our results indicate that the conformation of α-synuclein is linked to the aggregation of protein in cells. They also provide support for a therapeutic strategy of targeting specific conformations of the protein to suppress or control its aggregation.
Author(s): Moree B, Yin G, Lazaro DF, Munari F, Strohaker T, Giller K, Becker S, Outeiro TF, Zweckstetter M, Salafsky J
Publication type: Article
Publication status: Published
Journal: Journal of Biological Chemistry
Online publication date: 22/09/2015
Acceptance date: 01/01/1900
ISSN (print): 0021-9258
ISSN (electronic): 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology Inc.
PubMed id: 26396193
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