NMR structural studies of protein folding during biosynthesis on the ribosome (360G-Wellcome-203765_Z_16_A)

Proteins must fold into their tertiary structure in order to function. This complex process has been well studied over recent decades. However, most of these studies rely on small isolated proteins; protein folding inside of cells can be very different. In cells during translation, the ribosome synthesises proteins by adding amino acids to the growing polypeptide chain, this eventually extends out of the ribosome tunnel and can can begin to fold while still being synthesised; representing a major difference between historical folding studies and the real picture inside cells. In our lab we aim to characterise the process of protein folding on the ribosome. We are especially interested in how the ribosome may aid proteins to fold efficiently. To do this we use Nuclear Magnetic Resonance (NMR) spectroscopy to generate structural information of proteins attached to ribosomes alongside Cryo Electron Microscopy and Molecular dynamics computer simulations. This PhD project will aim to fully characterise the structure and dynamics of a nascent chain attached to the ribosome using a variety of NMR experiments. We will then analyse a variety of proteins to try and understand why they fold at different points during translation.