title: Light-activated DNA binding in a designed allosteric protein.
abstract: An understanding of how allostery, the conformational coupling of distant functional sites, arises in highly evolvable systems is of considerable interest in areas ranging from cell biology to protein design and signaling networks. We reasoned that the rigidity and defined geometry of an alpha-helical domain linker would make it effective as a conduit for allosteric signals. To test this idea, we rationally designed 12 fusions between the naturally photoactive LOV2 domain from Avena sativa phototropin 1 and the Escherichia coli trp repressor. When illuminated, one of the fusions selectively binds operator DNA and protects it from nuclease digestion. The ready success of our rational design strategy suggests that the helical "allosteric lever arm" is a general scheme for coupling the function of two proteins.
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Strickland
authors.forename: Keith
authors.initials: K
authors.lastname: Moffat
authors.forename: Tobin R
authors.initials: TR
authors.lastname: Sosnick
mesh_terms: D000495:Allosteric Site / Q000235:genetics*; D018554:Avena / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D056931:Cryptochromes; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism*; D008027:Light; D008958:Models, Molecular; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins
chemical_list: D001426:Bacterial Proteins; D056931:Cryptochromes; D004247:DNA; D005420:Flavoproteins; D012097:Repressor Proteins; C027190:TRPR protein, E coli; D029968:Escherichia coli Proteins