Improved techniques that allow researchers to follow protein folding and maturation as it occurs in live human cells are reported in a paper published this week in Nature Chemical Biology. This work will have important implications for the way scientists think about basic cell processes as well as potentially providing new ways to understand misfolding pathologies such as Alzheimer’s disease.
Nuclear magnetic resonance (NMR) spectroscopy is an important biophysical technique that allows scientists to determine the structure and mobility of amino acids within proteins, and has previously been used to look at abundant proteins within a bacterial cell. However, many human proteins require helper proteins or special environmental conditions that are not present in bacterial cells, and thus bacterial cells cannot provide a true picture of protein folding. Lucia Banci, Radu Aricescu and colleagues develop improved techniques which mean that NMR can be extended to human cells, allowing them to follow the proper folding of the critical antioxidant protein superoxide dismutase 1 (SOD1). The authors find that, as expected, the helper protein CCS is required to insert the correct metals in SOD1, but surprisingly, this step is not dependent on the formation of neighboring disulfide bonds, as anticipated from experiments done with purified proteins.