During protein biosynthesis, nascent polypeptide chains emerge from the ribosome’s exit tunnel and face a branch-point in which they have their first opportunity to either fold productively to adopt their 3D structure or misfold and form aberrant structure. The use of NMR spectroscopy on ribosomes and ribosome-nascent chain complexes (RNCs) is providing detailed structural and dynamic insights of the conformations sampled by nascent polypeptide chains while they are being synthesised on the ribosome. By producing in-vivo derived RNCs in which the nascent polypeptide chain is selectively isotopically labelled, our work is allowing us to use NMR to follow at a residue specific level, the co-translational emergence and folding of proteins of different topologies [1,2].
We present our structural studies in which are investigating the two proteins, an immunoglobulin domain [2] and an intrinsically disordered protein, alpha-synuclein [3]. Our emerging work describes the types of intermediate structures that are sampled, the role of the ribosomal surface and how the ribosome-associated molecular chaperone trigger factor, which interacts with the nascent chain, affects protein folding. Recent strides in examining the relationship between protein biosynthesis, and folding and misfolding processes will also be discussed.