title: The amino-terminal helix modulates light-activated conformational changes in AsLOV2.
abstract: The mechanism of light-triggered conformational change and signaling in light-oxygen-voltage (LOV) domains remains elusive in spite of extensive investigation and their use in optogenetic studies. The LOV2 domain of Avenasativa phototropin 1 (AsLOV2), a member of the Per-Arnt-Sim (PAS) family, contains a flavin mononucleotide chromophore that forms a covalent bond with a cysteine upon illumination. This event leads to the release of the carboxy-terminal Jα helix, the biological output signal. Using mutational analysis, circular dichroism, and NMR, we find that the largely ignored amino-terminal helix is a control element in AsLOV2's light-activated conformational change. We further identify a direct amino-to-carboxy-terminal "input-output" signaling pathway. These findings provide a framework to rationalize the LOV domain architecture, as well as the signaling mechanisms in both isolated and tandem arrangements of PAS domains. This knowledge can be applied in engineering LOV-based photoswitches, opening up new design strategies and improving existing ones.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Josiah P
authors.initials: JP
authors.lastname: Zayner
authors.forename: Chloe
authors.initials: C
authors.lastname: Antoniou
authors.forename: Tobin R
authors.initials: TR
authors.lastname: Sosnick
mesh_terms: D018554:Avena / Q000737:chemistry*; D005486:Flavin Mononucleotide / Q000737:chemistry; D008027:Light; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D056949:Phototropins / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D056949:Phototropins; D005486:Flavin Mononucleotide