title: Dynamic switching mechanisms in LOV1 and LOV2 domains of plant phototropins.
abstract: LOV domains are the light-sensitive portion of plant phototropins. They absorb light through a flavin cofactor, photochemically form a covalent bond between the chromophore and a cysteine residue in the protein, and proceed to mediate activation of an attached kinase domain. Although the photoreaction itself is now well-characterized experimentally and computationally, it is still unclear how the formation of the adduct leads to kinase activation. We have performed molecular dynamics simulations on the LOV1 domain of Chlamydomonas reinhardtii and the LOV2 domain of Avena sativa, both before and after the photoreaction, to answer this question. The extensive simulations, over 240 ns in duration, reveal significant differences in how the LOV1 and LOV2 domains respond to photoactivation. The simulations indicate that LOV1 activation is likely caused by a change in hydrogen bonding between protein and ligand that destabilizes a highly conserved salt bridge, whereas LOV2 activation seems to result from a change in the flexibility of a set of protein loops. Results of electrostatics calculations, principal component analysis, sequence alignments, and root mean-square deviation analysis corroborate the above findings.
authors.affiliation: Center for Biophysics and Computational Biology, Beckman Institute, and Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Lydia
authors.initials: L
authors.lastname: Freddolino
authors.forename: Markus
authors.initials: M
authors.lastname: Dittrich
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D003198:Computer Simulation; D056931:Cryptochromes; D005420:Flavoproteins / Q000737:chemistry* / Q000528:radiation effects*; D008027:Light; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry* / Q000528:radiation effects*; D011487:Protein Conformation / Q000528:radiation effects; D017434:Protein Structure, Tertiary / Q000528:radiation effects
chemical_list: D056931:Cryptochromes; D005420:Flavoproteins; D010940:Plant Proteins