title: Phosphorylation drives a dynamic switch in serine/arginine-rich proteins.
abstract: Serine/arginine-rich (SR) proteins are important players in RNA metabolism and are extensively phosphorylated at serine residues in RS repeats. Here, we show that phosphorylation switches the RS domain of the serine/arginine-rich splicing factor 1 from a fully disordered state to a partially rigidified arch-like structure. Nuclear magnetic resonance spectroscopy in combination with molecular dynamics simulations revealed that the conformational switch is restricted to RS repeats, critically depends on the phosphate charge state and strongly decreases the conformational entropy of RS domains. The dynamic switch also occurs in the 100 kDa SR-related protein hPrp28, for which phosphorylation at the RS repeat is required for spliceosome assembly. Thus, a phosphorylation-induced dynamic switch is common to the class of serine/arginine-rich proteins and provides a molecular basis for the functional redundancy of serine/arginine-rich proteins and the profound influence of RS domain phosphorylation on protein-protein and protein-RNA interactions.
authors.affiliation: Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
authors.forename: Shengqi
authors.initials: S
authors.lastname: Xiang
authors.forename: Vytautas
authors.initials: V
authors.lastname: Gapsys
authors.forename: Hai-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Sergey
authors.initials: S
authors.lastname: Bessonov
authors.forename: He-Hsuan
authors.initials: HH
authors.lastname: Hsiao
authors.forename: Sina
authors.initials: S
authors.lastname: Möhlmann
authors.forename: Volker
authors.initials: V
authors.lastname: Klaukien
authors.forename: Ralf
authors.initials: R
authors.lastname: Ficner
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lührmann
authors.forename: Bert
authors.initials: B
authors.lastname: de Groot
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D001120:Arginine / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D056004:Molecular Dynamics Simulation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D012694:Serine / Q000737:chemistry* / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors
chemical_list: D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D012694:Serine; D001120:Arginine