Allosteric Networks on Demand

Science Signaling  21 Oct 2008:
Vol. 1, Issue 42, pp. ec365
DOI: 10.1126/scisignal.142ec365

Protein function depends not only on local interactions between amino acids but also on communication between separated sites. For example, the activity of a protein may be regulated by ligand binding to a distant surface. This raises the possibility that the allosteric networks in two proteins could be connected so that the activity of one protein regulates the activity of the other. Lee et al. now report the construction of such a chimera. They used statistical coupling analysis (SCA) to identify allosteric networks in a light-sensing Per/Arnt/Sim (PAS) signaling domain and in the enzyme dihydrofolate reductase (DHFR). Based on this information, they engineered PAS-DHFR chimeras aimed to link the two networks. With no optimization, one chimera displayed a modest light-dependent catalytic activity, providing a proof of concept for engineering protein complexes with coupled activities.

J. Lee, M. Natarajan, V. C. Nashine, M. Socolich, T. Vo, W. P. Russ, S. J. Benkovic, R. Ranganathan, Surface sites for engineering allosteric control in proteins. Science 322, 438-442 (2008). [Abstract] [PubMed]