Structure of the TPR Domain of p67phox in Complex with Rac·GTP
Open accessAbstract
p67phox is an essential part of the NADPH oxidase, a multiprotein enzyme complex that produces superoxide ions in response to microbial infection. Binding of the small GTPase Rac to p67phox is a key step in the assembly of the active enzyme complex. The structure of Rac.GTP bound to the N-terminal TPR (tetratricopeptide repeat) domain of p67phox reveals a novel mode of Rho family/effector interaction and explains the basis of GTPase specificity. Complex formation is largely mediated by an insertion between two TPR motifs, suggesting an unsuspected versatility of TPR domains in target recognition and in their more general role as scaffolds for the assembly of multiprotein complexes.
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p67phox is not a downstream effector of wildtype Cdc42, but Cdc42-to-Rac substitutions at positions 27 and 30 (K27A and S30G) in Cdc42 allow p67phox to serve as an effector of the resulting mutant Cdc42.
“p67 phox is not a downstream effector of wildtype Cdc42, however, Cdc42-to-Rac substitutions at positions 27 and 30 (K27A and S30G) in Cdc42 allows p67 phox to serve as an effector of the resulting mutant Cdc42 (49,50).”
From Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors (2008) · cites this paper as [50]
Previous structural and biochemical studies indicated that divergent amino acids at positions 27 and 30 in the switch 1 region of Rac are important for specific recognition and recruitment of its downstream effector p67phox.
“Moreover, previous structural and biochemical studies indicated that divergent amino acids at positions 27 and 30 in the switch 1 region of Rac are important for specific recognition and recruitment of its downstream effector p67 phox , a component of the NADPH oxidase (49,50).”
From Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors (2008) · cites this paper as [50]
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References 64 · Cited by 311
Research works printed but not linked: 22
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- Authors
- Lapouge, K., Smith, S. J. M., Walker, P. A., Gamblin, S. J., Smerdon, S. J., & Rittinger, K.
- Affiliations
- National Institute for Medical Research (GB)
- Corresponding author
- Rittinger, Katrin
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 6
- Issue
- 4
- Pages
- 899-907
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1975544278
- Cited by
- 311
- References
- 64
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 10 · 2022: 6 · 2021: 16 · 2020: 11 · 2019: 12 · 2018: 6 · 2017: 4 · 2016: 8 · 2015: 11 · 2014: 12 · 2013: 12 · 2012: 7
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- ePubs (Science and Technology Facilities Council, Research Councils UK) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- p67phox, Rac GTPase, tetratricopeptide repeat domain, NADPH oxidase, protein complex formation, superoxide production, scaffolds
- MeSH terms
- RAC2 GTP-Binding Protein, Amino Acid Sequence, Binding Sites, Calorimetry, Guanosine Triphosphate, Humans, Models, Molecular, Molecular Sequence Data, NADPH Dehydrogenase, Phosphoproteins, Recombinant Proteins, Thermodynamics, Sequence Alignment, Sequence Homology, Amino Acid, Protein Structure, Secondary, Repetitive Sequences, Amino Acid, rac GTP-Binding Proteins
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