Weak protein–protein interactions as probed by NMR spectroscopy

Weak protein–protein interactions (PPIs) are fundamental to many cellular processes, such as reversible cell–cell contact, rapid enzyme turnover and transient assembly and/or reassembly of large signaling complexes. However, structural and functional characterizations of weak PPIs have been technically challenging and lagged behind those for strong PPIs. Here, we describe nuclear magnetic resonance (NMR) spectroscopy as a highly effective tool for unraveling the atomic details of weak PPIs. We highlight the recent advances of how NMR can be used to rapidly detect and structurally determine extremely weak PPIs (Kd>10−4 M). Coupled with functional approaches, NMR has the potential to look into a wide variety of biologically important weak PPIs at the detailed molecular level, thereby facilitating a thorough view of how proteins function in living cells.