Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase

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Interaction of the Rho-ADP-ribosylating C3 exoenzyme with RalA.

RhoA, -B, and -C are ADP-ribosylated and biologically inactivated by Clostridium botulinum C3 exoenzyme and related C3-like transferases. We report that RalA GTPase, which is not ADP-ribosylated by C3, inhibits ADP-ribosylation of RhoA by C3 from C. botulinum (C3bot), Clostridium limosum (C3lim), and Bacillus cereus (C3cer) but not from Staphylococcus aureus (C3stau) in human platelet membranes...

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Structural basis of Rho GTPase recognition by C3 exoenzyme

C3 exoenzyme is a mono-ADPribosyltransferase (ART) that catalyzes transfer of an ADP-ribose moiety from NAD to Rho GTPases. C3 has long been used to study the diverse regulatory functions of Rho GTPases. How C3 recognizes its substrate and ADP-ribosylation proceeds are still poorly understood. Crystal structures of C3-RhoA complex reveal that C3 recognizes RhoA via switch I, switch II and inter...

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The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg–Gly–Asp motif

The Rho ADP-ribosylating C3 exoenzyme (C3bot) is a bacterial protein toxin devoid of a cell-binding or -translocation domain. Nevertheless, C3 can efficiently enter intact cells, including neurons, but the mechanism of C3 binding and uptake is not yet understood. Previously, we identified the intermediate filament vimentin as an extracellular membranous interaction partner of C3. However, uptak...

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Uptake of Clostridium botulinum C3 Exoenzyme into Intact HT22 and J774A.1 Cells

The Clostridium botulinum C3 exoenzyme selectively ADP-ribosylates low molecular weight GTP-binding proteins RhoA, B and C. This covalent modification inhibits Rho signaling activity, resulting in distinct actin cytoskeleton changes. Although C3 exoenzyme has no binding, the translocation domain assures that C3 enters cells and acts intracellularly. C3 uptake is thought to occur due to the high...

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Clostridium Botulinum C3 Exoenzyme: Rho-Inactivating Tool in Cell Biology and a Neurotrophic Agent

C3 exoenzyme from Clostridium botulinum is the prototype of bacterial ADP-ribosyltransferases, which selectively modifies the Rho isoforms RhoA, RhoB and RhoC by covalent attachment of an ADP-ribose moiety. ADPribosylation results in inactivation of cellular functions of Rho. Because of its highly restricted substrate specificity, C3 is an established tool in cell biology; to this end C3 is app...

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ژورنال

عنوان ژورنال: Proceedings of the National Academy of Sciences

سال: 2005

ISSN: 0027-8424,1091-6490

DOI: 10.1073/pnas.0501525102