title: Structural basis for the NAD-hydrolysis mechanism and the ARTT-loop plasticity of C3 exoenzymes.
abstract: C3-like exoenzymes are ADP-ribosyltransferases that specifically modify some Rho GTPase proteins, leading to their sequestration in the cytoplasm, and thus inhibiting their regulatory activity on the actin cytoskeleton. This modification process goes through three sequential steps involving NAD-hydrolysis, Rho recognition, and binding, leading to Rho ADP-ribosylation. Independently, three distinct residues within the ARTT loop of the C3 exoenzymes are critical for each of these steps. Supporting the critical role of the ARTT loop, we have shown previously that it adopts a distinct conformation upon NAD binding. Here, we present seven wild-type and ARTT loop-mutant structures of C3 exoenzyme of Clostridium botulinum free and bound to its true substrate, NAD, and to its NAD-hydrolysis product, nicotinamide. Altogether, these structures expand our understanding of the conformational diversity of the C3 exoenzyme, mainly within the ARTT loop.
authors: Institut Curie, Centre de Recherche, Paris F-75248, France. julie.Menetrey@curie.fr
authors: Julie
authors: J
authors: Ménétrey
authors: Gilles
authors: G
authors: Flatau
authors: Patrice
authors: P
authors: Boquet
authors: André
authors: A
authors: Ménez
authors: Enrico A
authors: EA
authors: Stura
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry* / Q000235:genetics; D019943:Amino Acid Substitution; D001216:Asparagine / Q000737:chemistry; D001665:Binding Sites / Q000235:genetics; D001905:Botulinum Toxins / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D018698:Glutamic Acid / Q000737:chemistry; D006868:Hydrolysis; D009154:Mutation; D009243:NAD / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D009243:NAD; D018698:Glutamic Acid; D001216:Asparagine; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins