Conditional Membrane Proteins: Solution NMR Studies of Structure, Dynamics, and Function

The focus of this article is the application of solution NMR methods to the studies of conditional peripheral membrane proteins, CPMPs. CPMPs occur as individual domains in host proteins that are involved in signal transduction at the endo-membranes. Owing to their amphiphilic nature, CPMPs are able to reversibly associate with membranes in response to Ca2(+),lipid second messengers, and other membrane components. While extensive structural work has been conducted on the apo forms of these proteins, their dynamic properties and interactions with membranes are not well explored. NMR spectroscopy enables us to study the residue-specific dynamics of CPMPs on multiple timescales and to probe their interactions with membranes/ lipid ligands through the incorporation of NMR-compatible membrane mimics. In this article, we illustrate the application of solution NMR methods using two types of CPMPs, the conserved region 1 (C1) and conserved region 2 (C2) domains from Protein Kinase C. We also discuss current challenges in the field and outline future directions.