2a78
From Proteopedia
(New page: 200px<br /> <applet load="2a78" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a78, resolution 1.810Å" /> '''Crystal structure ...) |
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caption="2a78, resolution 1.810Å" /> | caption="2a78, resolution 1.810Å" /> | ||
'''Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme'''<br /> | '''Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme'''<br /> | ||
==Overview== | ==Overview== | ||
| - | C3 exoenzymes from bacterial pathogens ADP-ribosylate and inactivate | + | C3 exoenzymes from bacterial pathogens ADP-ribosylate and inactivate low-molecular-mass GTPases of the Rho subfamily. Ral, a Ras subfamily GTPase, binds the C3 exoenzymes from Clostridium botulinum and C. limosum with high affinity without being a substrate for ADP ribosylation. In the complex, the ADP-ribosyltransferase activity of C3 is blocked, while binding of NAD and NAD-glycohydrolase activity remain. Here we report the crystal structure of C3 from C. botulinum in a complex with GDP-bound RalA at 1.8 A resolution. C3 binds RalA with a helix-loop-helix motif that is adjacent to the active site. A quaternary complex with NAD suggests a mode for ADP-ribosyltransferase inhibition. Interaction of C3 with RalA occurs at a unique interface formed by the switch-II region, helix alpha3 and the P loop of the GTPase. C3-binding stabilizes the GDP-bound conformation of RalA and blocks nucleotide release. Our data indicate that C. botulinum exoenzyme C3 is a single-domain toxin with bifunctional properties targeting Rho GTPases by ADP ribosylation and Ral by a guanine nucleotide dissociation inhibitor-like effect, which blocks nucleotide exchange. |
==About this Structure== | ==About this Structure== | ||
| - | 2A78 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Clostridium_botulinum_d_phage Clostridium botulinum d phage] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2A78 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Clostridium_botulinum_d_phage Clostridium botulinum d phage] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A78 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: rho]] | [[Category: rho]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:24:16 2008'' |
Revision as of 14:24, 21 February 2008
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Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme
Overview
C3 exoenzymes from bacterial pathogens ADP-ribosylate and inactivate low-molecular-mass GTPases of the Rho subfamily. Ral, a Ras subfamily GTPase, binds the C3 exoenzymes from Clostridium botulinum and C. limosum with high affinity without being a substrate for ADP ribosylation. In the complex, the ADP-ribosyltransferase activity of C3 is blocked, while binding of NAD and NAD-glycohydrolase activity remain. Here we report the crystal structure of C3 from C. botulinum in a complex with GDP-bound RalA at 1.8 A resolution. C3 binds RalA with a helix-loop-helix motif that is adjacent to the active site. A quaternary complex with NAD suggests a mode for ADP-ribosyltransferase inhibition. Interaction of C3 with RalA occurs at a unique interface formed by the switch-II region, helix alpha3 and the P loop of the GTPase. C3-binding stabilizes the GDP-bound conformation of RalA and blocks nucleotide release. Our data indicate that C. botulinum exoenzyme C3 is a single-domain toxin with bifunctional properties targeting Rho GTPases by ADP ribosylation and Ral by a guanine nucleotide dissociation inhibitor-like effect, which blocks nucleotide exchange.
About this Structure
2A78 is a Protein complex structure of sequences from Clostridium botulinum d phage and Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme., Pautsch A, Vogelsgesang M, Trankle J, Herrmann C, Aktories K, EMBO J. 2005 Oct 19;24(20):3670-80. Epub 2005 Sep 22. PMID:16177825
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