Engineering allosteric protein switches by domain insertion.
Domain insertion is proving to be an effective way to construct hybrid proteins exhibiting switch-like behavior. In this strategy, two existing domains, the first exhibiting a signal recognition function and the second containing the function to be modulated, are fused such that the recognition of the signal by the first domain is transmitted to the second domain, thereby modulating its activity. Recent directed evolution experiments indicate that the structural space comprised of the recombination of unrelated protein domains may be rich in switching behavior, particularly when the circular permutation of domains is also employed. This bodes well for potential basic science, sensing and therapeutic applications of molecular switches.
Ostermeier
Marc
M
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA. oster@jhu.edu
D000494:Allosteric Regulation; D019677:Artificial Gene Fusion / Q000379:methods; D015374:Biosensing Techniques; D004798:Enzymes / Q000096:biosynthesis / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D008024:Ligands; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D019154:Protein Splicing; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics
D004798:Enzymes; D008024:Ligands; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins