title: Optical control of protein-protein interactions via blue light-induced domain swapping.
abstract: The design of new optogenetic tools for controlling protein function would be facilitated by the development of protein scaffolds that undergo large, well-defined structural changes upon exposure to light. Domain swapping, a process in which a structural element of a monomeric protein is replaced by the same element of another copy of the same protein, leads to a well-defined change in protein structure. We observe domain swapping in a variant of the blue light photoreceptor photoactive yellow protein in which a surface loop is replaced by a well-characterized protein-protein interaction motif, the E-helix. In the domain-swapped dimer, the E-helix sequence specifically binds a partner K-helix sequence, whereas in the monomeric form of the protein, the E-helix sequence is unable to fold into a binding-competent conformation and no interaction with the K-helix is seen. Blue light irradiation decreases the extent of domain swapping (from Kd = 10 μM to Kd = 300 μM) and dramatically enhances the rate, from weeks to <1 min. Blue light-induced domain swapping thus provides a novel mechanism for controlling of protein-protein interactions in which light alters both the stability and the kinetic accessibility of binding-competent states.
authors.affiliation: Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, ON M5S 3H6, Canada.
authors.forename: Jakeb M
authors.initials: JM
authors.lastname: Reis
authors.forename: Darcy C
authors.initials: DC
authors.lastname: Burns
authors.forename: G Andrew
authors.initials: GA
authors.lastname: Woolley
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation / Q000379:methods*; D020283:Photoreceptors, Microbial / Q000737:chemistry* / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D020283:Photoreceptors, Microbial; C050162:photoactive yellow protein, Bacteria