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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
Structure of the TPR domain of p67phox in complex with Rac.GTP
K Lapouge1, S J Smith, P A Walker
1Division of Protein Structure, National Institute for Medical Research, London, United Kingdom.
Molecular Cell
|November 25, 2000
Summary
p67phox, a key NADPH oxidase component, binds the small GTPase Rac. This interaction, crucial for superoxide production against microbes, reveals novel Rho family/effector binding and GTPase specificity mechanisms.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- p67phox is essential for NADPH oxidase function, which generates superoxide ions during microbial infection.
- The binding of the small GTPase Rac to p67phox is a critical event for assembling the active NADPH oxidase enzyme complex.
Purpose of the Study:
- To elucidate the structural basis of Rac.GTP binding to the N-terminal tetratricopeptide repeat (TPR) domain of p67phox.
- To understand the novel mode of Rho family/effector interaction and the specificity of GTPase binding.
Main Methods:
- X-ray crystallography to determine the structure of the Rac.GTP/p67phox N-terminal TPR domain complex.
Main Results:
- The structure reveals a novel interaction mode between Rac GTPase and the TPR domain of p67phox.
- GTPase specificity is explained by the observed binding interface.
- Complex formation is mediated by an insertion between TPR motifs, highlighting TPR domain versatility.
Conclusions:
- The N-terminal TPR domain of p67phox utilizes a unique mechanism for Rac recognition and binding.
- This interaction is crucial for the assembly and activation of the NADPH oxidase complex.
- TPR domains exhibit unexpected versatility in target recognition and serve as scaffolds in multiprotein complex assembly.
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