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

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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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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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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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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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C3 exoenzyme from Clostridium botulinum: structure of a tetragonal crystal form and a reassessment of NAD-induced flexure.

C3 exoenzyme from Clostridium botulinum (C3bot1) ADP-ribosylates and thereby inactivates Rho A, B and C GTPases in mammalian cells. The structure of a tetragonal crystal form has been determined by molecular replacement and refined to 1.89 A resolution. It is very similar to the apo structures determined previously from two different monoclinic crystal forms. An objective reassessment of availa...

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ژورنال

عنوان ژورنال: The Open Toxinology Journal

سال: 2013

ISSN: 1875-4147

DOI: 10.2174/1875414701003010019