2A78

Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme

Summary for 2A78

• Entry DOI: 10.2210/pdb2a78/pdb
• Related: 1G24 1u8y 1u8z 1u90 1uad 2bov
• Descriptor: Ras-related protein Ral-A, Mono-ADP-ribosyltransferase C3, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: exoenzyme c3, bacterial adp-ribosyltransferase, ral, rho, gdp-binding, protein binding-transferase complex, protein binding/transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane ; Lipid- anchor ; Cytoplasmic side: P11233; Secreted: P15879
• Total number of polymer chains: 2
• Total formula weight: 45825.58

Authors

Pautsch, A.,Vogelsgesang, M.,Trankle, J.,Herrmann, C.,Aktories, K. (deposition date: 2005-07-05, release date: 2005-10-11, Last modification date: 2023-08-23)

Primary citation

Pautsch, A.,Vogelsgesang, M.,Trankle, J.,Herrmann, C.,Aktories, K.
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.
Embo J., 24:3670-3680, 2005

PubMed Abstract: 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.

PubMed: 16177825
DOI: 10.1038/sj.emboj.7600813

Experimental method

X-RAY DIFFRACTION (1.81 Å)