Chapter 13: Structural Biology in Cells by In-cell NMR

In-cell NMR has the potential to study protein structure and dynamics within a cell. In this chapter, the history of in-cell NMR and the various in-cell NMR methods established along with their applications with a focus on chaperones is discussed. A comprehensive summary of previously studied proteins in table form is presented. So far 39 proteins, which are presented in this chapter in a comprehensive summary, have been studied by in-cell NMR in bacteria, yeast, insect cells, Xenopus laevis oocytes, and mammalian cell systems. It is our feeling that the number of proteins is far below what one would expect for a method with such potential and developed more than 20 years ago. This might indicate great prospects for future improvements. The methods include either protein overexpression or stable-isotope protein delivery termed transexpression. To give an example of dynamics and protein–protein interactions studied by in-cell NMR, we described in detail the intrinsically disordered protein α-synuclein and its transient interaction with chaperones.