An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins.

ABSTRACT: The C3-like toxins are single-domain proteins that represent a minimal mono-ADP-ribosyl transferase (mART) enzyme with a simple model scaffold for the entire cholera toxin (CT)-group. These proteins possess a single (A-domain) that modifies Rho proteins. In contrast, C2-like toxins require a binding/translocation partner (B-component) for intoxication. These are A-only toxins that contain the E-x-E motif, modify G-actin, but are two-domains with a C-domain possessing enzymatic activity. The N-domain of the C2-like toxins is unstructured, and its function is currently unknown. A sequence-structure-function comparison was performed on the N-terminal region of the mART domain of the enzymatic component of the CT toxin group in the CATCH fold (3.90.210.10). Special consideration was given to the N-domain distal segment, the ?-lobe (?1-?4), and its different roles in these toxin sub-groups. These results show that the role of the N-terminal ?-lobe is to provide a suitable configuration (i) of the ?2-?3 helices to feature the ?3-motif that has a role in NAD+ substrate binding and possibly in the interaction with the protein target; (ii) the ?3-?4 helices to provide the ?3/4-loop with protein-protein interaction capability; and (iii) the ?1-Ntail that features specialized motif(s) according to the toxin type (A-only or A-B toxins) exhibiting an effect on the catalytic activity via the ARTT-loop, with a role in the inter-domain stability, and with a function in the binding and/or translocation steps during the internalization process.

SUBMITTER: Lugo MR 

PROVIDER: S-EPMC6628389 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature