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Publication Abstract from PubMed

C3larvin toxin is a new member of the C3 class of the mono-ADP-ribosyltransferase toxin family. The C3 toxins are known to covalently modify small G-proteins, e.g. RhoA, impairing their function, and serving as virulence factors for an offending pathogen. A full-length X-ray structure of C3larvin (2.3 A) revealed that the characteristic mixed alpha/beta fold consists of a central beta-core flanked by two helical regions. Topologically, the protein can be separated into N and C lobes, each formed by a beta-sheet and an alpha-motif, and connected by exposed loops involved in the recognition, binding, and catalysis of the toxin/enzyme, i.e. the ADP-ribosylation turn-turn and phosphate-nicotinamide PN loops. Herein, we provide two new C3larvin X-ray structures and present a systematic study of the toxin dynamics by first analyzing the experimental variability of the X-ray data-set followed by contrasting those results with theoretical predictions based on Elastic Network Models (GNM and ANM). We identify residues that participate in the stability of the N-lobe, putative hinges at loop residues, and energy-favored deformation vectors compatible with conformational changes of the key loops and 3D-subdomains (N/C-lobes), among the X-ray structures. We analyze a larger ensemble of known C3bot1 conformations and conclude that the characteristic 'crab-claw' movement may be driven by the main intrinsic modes of motion. Finally, via computational simulations, we identify harmonic and anharmonic fluctuations that might define the C3larvin 'native state.' Implications for docking protocols are derived.

Structural variability of C3larvin toxin. Intrinsic dynamics of the alpha/beta fold of the C3-like group of mono-ADP-ribosyltransferase toxins.,Lugo MR, Ravulapalli R, Dutta D, Rod Merrill A J Biomol Struct Dyn. 2016 Dec;34(12):2537-2560. Epub 2016 Apr 21. PMID:26610041^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.