title: Conformational plasticity is crucial for C3-RhoA complex formation by ARTT-loop.
abstract: ADP-ribosylation is an important post-translational protein modification catalyzed by bacterial toxins and eukaryotic endogenous ADP-ribosyltransferases. Bacterial binary toxins and C3-like toxins recognize and ADP-ribosylate actin Arg177 and RhoA Asn41, respectively. Structural and mutational studies have identified an ADP-ribosylating turn-turn loop (ARTT-loop) that has been implicated in substrate specificity and recognition, although it has not been verified. Recently, we determined the crystal structure of the C3 exoenzyme-RhoA complex. The complex structure shows how C3 recognizes Rho GTPase and provides the first structural evidence for RhoA recognition by the ARTT-loop. The complex formation mediated by the ARTT-loop is through the intrinsic plasticity of C3 and RhoA. C3 changes the conformations of both the phosphate nicotinamide-loop and the ARTT-loop by NAD(+) and RhoA binding, respectively. In contrast, RhoA changes the conformations of switch I and II regions upon C3 binding with a particular conformation, irrespective of the bound nucleotide (GTP or GDP).
authors.affiliation: Department of Bioresource and Environmental Sciences, Faculty of Life Sciences and Structural Biology Research Center, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan tsuge@cc.kyoto-su.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tsuge
authors.affiliation: Department of Bioresource and Environmental Sciences, Faculty of Life Sciences and Structural Biology Research Center, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Bioresource and Environmental Sciences, Faculty of Life Sciences and Structural Biology Research Center, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Tsurumura
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry* / Q000378:metabolism*; D001905:Botulinum Toxins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D020742:rhoA GTP-Binding Protein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein
keywords: ADP-ribosylation; ARTT-loop; C3 exoenzyme; RhoA; complex structure; conformational plasticity