National Academy of Sciences, Proceedings of the National Academy of Sciences, 18(113), p. 5012-5017, 2016
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Significance Protein biosynthesis is carried out by ribosomes, the macromolecular machines present in all kingdoms of life. Aided by molecular chaperones, nascent proteins can begin to fold while emerging from the ribosome. Achieving their native fold, and avoiding misfolding, is thereby crucial for the fate of all newly synthesized proteins. The molecular details of this fundamental process, however, are poorly understood. In this work we develop a combined NMR and molecular simulation approach to characterize the behavior during biosynthesis of α-synuclein (αSyn), an intrinsically disordered protein associated with Parkinson’s disease. The detailed interactions of αSyn with the ribosome surface and with trigger factor, a ribosome-associated chaperone, reveal the first steps of how a nascent chain emerges from the ribosome.