Facilitated Protein Association via Engineered Target Search Pathways Visualized by Paramagnetic NMR Spectroscopy
 

Facilitated Protein Association via Engineered Target Search Pathways Visualized by Paramagnetic NMR Spectroscopy

Publication date: Available online 17 May 2018
Source:Structure</br>
Author(s): So Young An, Eun-Hee Kim, Jeong-Yong Suh</br>
Proteins assemble to form functional complexes via the progressive evolution of nonspecific complexes formed by transient encounters. This target search process generally involves multiple routes that lead the initial encounters to the final complex. In this study, we have employed NMR paramagnetic relaxation enhancement to visualize the encounter complexes between histidine-containing phosphocarrier protein and the N-terminal domain of enzyme I and*demonstrate that protein association can be significantly enhanced by engineering on-pathways. Specifically, mutations in surface charges away from*the binding interface can elicit new on-pathway encounter complexes, increasing their binding affinity by an order of magnitude. The structure of these encounter complexes indicates that such on-pathways extend the built-in target search process of the native protein complex. Furthermore, blocking on-pathways by countering mutations reverts their binding affinity. Our study thus illustrates that protein interactions can be engineered by rewiring the target search process.
Graphical abstract

http://origin-ars.els-cdn.com/conten...301345-fx1.jpg</br> Teaser

An et*al. investigate the target search process during protein-protein interactions that lead transient nonspecific encounters into the final specific complex. Paramagnetic NMR spectroscopy effectively visualizes the target search pathways that are engineered to facilitate protein association.</br>
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