An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/6/365 |
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| author | Miguel R. Lugo A. Rod Merrill |
| author_facet | Miguel R. Lugo A. Rod Merrill |
| author_sort | Miguel R. Lugo |
| collection | DOAJ |
| description | 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 α-lobe (α<sub>1</sub>−α<sub>4</sub>), and its different roles in these toxin sub-groups. These results show that the role of the N-terminal α-lobe is to provide a suitable configuration (i) of the α<sub>2</sub>−α<sub>3</sub> helices to feature the α3-motif that has a role in NAD<sup>+</sup> substrate binding and possibly in the interaction with the protein target; (ii) the α<sub>3</sub>−α<sub>4</sub> helices to provide the α<sub>3/4</sub>-loop with protein-protein interaction capability; and (iii) the α<sub>1</sub>-N<sub>tail</sub> 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. |
| first_indexed | 2024-04-11T20:40:14Z |
| format | Article |
| id | doaj.art-eab055346de04b96a743b3ce80d0f13e |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T20:40:14Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-eab055346de04b96a743b3ce80d0f13e2022-12-22T04:04:14ZengMDPI AGToxins2072-66512019-06-0111636510.3390/toxins11060365toxins11060365An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase ToxinsMiguel R. Lugo0A. Rod Merrill1Department of Molecular and Cellular Biology, University of Guelph, Guelph N1G 2W1, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph N1G 2W1, CanadaThe 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 α-lobe (α<sub>1</sub>−α<sub>4</sub>), and its different roles in these toxin sub-groups. These results show that the role of the N-terminal α-lobe is to provide a suitable configuration (i) of the α<sub>2</sub>−α<sub>3</sub> helices to feature the α3-motif that has a role in NAD<sup>+</sup> substrate binding and possibly in the interaction with the protein target; (ii) the α<sub>3</sub>−α<sub>4</sub> helices to provide the α<sub>3/4</sub>-loop with protein-protein interaction capability; and (iii) the α<sub>1</sub>-N<sub>tail</sub> 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.https://www.mdpi.com/2072-6651/11/6/365mono-ADP-ribosylation toxinsC3-like toxinsC2-like toxinsADP-ribosylationCT-toxinstarget substrate motifsN-terminal α-lobe |
| spellingShingle | Miguel R. Lugo A. Rod Merrill An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins Toxins mono-ADP-ribosylation toxins C3-like toxins C2-like toxins ADP-ribosylation CT-toxins target substrate motifs N-terminal α-lobe |
| title | An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins |
| title_full | An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins |
| title_fullStr | An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins |
| title_full_unstemmed | An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins |
| title_short | An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins |
| title_sort | in silico sequence structure function analysis of the n terminal lobe in ct group bacterial adp ribosyltransferase toxins |
| topic | mono-ADP-ribosylation toxins C3-like toxins C2-like toxins ADP-ribosylation CT-toxins target substrate motifs N-terminal α-lobe |
| url | https://www.mdpi.com/2072-6651/11/6/365 |
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