title: Post-translational environmental switch of RadA activity by extein-intein interactions in protein splicing.
abstract: Post-translational control based on an environmentally sensitive intervening intein sequence is described. Inteins are invasive genetic elements that self-splice at the protein level from the flanking host protein, the exteins. Here we show in Escherichia coli and in vitro that splicing of the RadA intein located in the ATPase domain of the hyperthermophilic archaeon Pyrococcus horikoshii is strongly regulated by the native exteins, which lock the intein in an inactive state. High temperature or solution conditions can unlock the intein for full activity, as can remote extein point mutations. Notably, this splicing trap occurs through interactions between distant residues in the native exteins and the intein, in three-dimensional space. The exteins might thereby serve as an environmental sensor, releasing the intein for full activity only at optimal growth conditions for the native organism, while sparing ATP consumption under conditions of cold-shock. This partnership between the intein and its exteins, which implies coevolution of the parasitic intein and its host protein may provide a novel means of post-translational control.
authors.affiliation: Department of Biological Sciences and RNA Institute, University at Albany, 1400 Washington Avenue, Albany, NY 12222, USA.
authors.forename: Natalya I
authors.initials: NI
authors.lastname: Topilina
authors.affiliation: Department of Biological Sciences and RNA Institute, University at Albany, 1400 Washington Avenue, Albany, NY 12222, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Novikova
authors.affiliation: Department of Biological Sciences and RNA Institute, University at Albany, 1400 Washington Avenue, Albany, NY 12222, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Stanger
authors.affiliation: Laboratory of Computational and Structural Biology, Division of Genetics, Wadsworth Center, NYS Department of Health and Department of Biomedical Sciences, University at Albany, CMS 2008, Biggs Lab, Empire State Plaza, PO Box 509, Albany, NY 12201-2002, USA.
authors.forename: Nilesh K
authors.initials: NK
authors.lastname: Banavali
authors.affiliation: Department of Biological Sciences and RNA Institute, University at Albany, 1400 Washington Avenue, Albany, NY 12222, USA mbelfort@albany.edu.
authors.forename: Marlene
authors.initials: M
authors.lastname: Belfort
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D047669:Exteins; D047668:Inteins; D008958:Models, Molecular; D009154:Mutation; D019154:Protein Splicing; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043902:Pyrococcus horikoshii / Q000235:genetics; D011938:Rec A Recombinases / Q000737:chemistry; D013696:Temperature
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C117252:RadA protein, archaeal; C100901:RadA protein, bacteria; D011938:Rec A Recombinases