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Structure of a bacterial toxin-activating acyltransferase
Nicholas P Greene1, Allister Crow1, Colin Hughes2
1Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Summary
Pathogenic bacteria use toxin-activating acyl-transferases (TAATs) to activate toxins. We determined the structure of a TAAT, revealing a new Gcn5-like N-acetyl transferase (GNAT) enzyme family crucial for bacterial pathogenesis.
Area of Science:
- Microbiology
- Structural Biology
- Enzymology
Background:
- Pathogenic Gram-negative bacteria secrete pore-forming toxins that are synthesized as inactive protoxins.
- Protoxin activation requires posttranslational acylation by specialized acyl-transferases in the bacterial cytosol, using acyl carrier protein (ACP).
- These toxins disrupt host cell signaling, leading to apoptosis and lysis.
Purpose of the Study:
- To determine the X-ray structure of a toxin-activating acyl-transferase (TAAT).
- To elucidate the structural and functional relationship of TAATs within the Gcn5-like N-acetyl transferase (GNAT) superfamily.
- To characterize the solution state and active site of TAATs.
Main Methods:
- X-ray crystallography (2.15-Å resolution) of Actinobacillus pleuropneumoniae ApxC.
- Small angle X-ray scattering (SAXS).
- Mutagenesis, cross-linking, and enzyme activity assays.
Main Results:
- The structure of ApxC, a 172-amino acid TAAT, was determined.
- Bacterial TAATs form a structurally homologous family, representing a distinct branch of the GNAT superfamily.
- Intermonomer interactions are mediated by an N-terminal α-helix, and the active site is a deep surface groove.
Conclusions:
- TAATs are a novel, structurally conserved family of GNAT enzymes essential for bacterial toxin activation.
- The structural insights provide a basis for understanding TAAT function and substrate interaction.
- This work expands the known diversity of the GNAT superfamily and its role in microbial pathogenesis.
Keywords:
X-ray crystallographyacyl carrier proteinacyltransferasehemolysinposttranslational modificationMore Related Videos
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