Co-Translational Protein Folding on the Ribosome: Using NMR Spectroscopy to Provide Structure and Dynamics of Ribosome-Nascent Chains.

Abstract

The folding processes of nascent chains are intricately linked to their chain elongation, which occurs in a vectorial manner as the N-terminal part of the nascent chain emerges from the ribosome [1]. The use of NMR spectroscopy on ribosome nascent-chain complexes (RNCs) is providing detailed structural insights of the conformations of protein chains while they are being created on the ribosome. By producing in-vivo derived RNCs in which the nascent polypeptide is selectively-labeled, our recent work has allowed us to use NMR to follow, at a residue-specific level, the co-translational folding processes of proteins of several topologies, specifically, an immunoglobulin(Ig) domain, of YFP (both by fluorescence and NMR) and of the intrinsically disordered protein, alpha-synuclein.New work is allowing us to describe the types of intermediates sampled during the vectorial emergence, the RNC interactions with the ribosome and also how the chaperone, the trigger factor, that interacts with the nascent chain, affect protein folding. Recent strides towards a detailed understanding of the relationship between biosynthesis and folding will be discussed.Recent references:1. Protein Folding on the Ribosome: Cabrita, L.D., Dobson, C.M., Christodoulou, J.∗ Current Opin Struct Biol (2010) 20, 33-45.2. Probing ribosome-nascent chain complexes produced in vivo by NMR spectroscopy: Cabrita, L.D., Hsu, S.-T. D., Launay, H., Dobson, C.M., Christodoulou, J.∗ P.N.A.S (2009) 106, 22239-44.3. New scenarios of protein folding can occur on the ribosome: O’Brien, E.P.,Christodoulou, J.,Vendruscolo, M.,Dobson, C.M. J. Am. Chem. Soc (2011) 133, 513-526.