Consensus in silico computational modelling of the p22phox subunit of the NADPH oxidase
Abstract
The p22(phox) protein is an essential subunit of the cytochrome b(558) of the NADPH oxidase (Nox) complex which by generating reactive oxygen species (ROS) plays important role in regulating cellular function. p22(phox) stabilises the Nox enzyme, assists in catalytic core maturation and in the meantime provides an anchoring site for cytosolic regulatory subunits to bind. However, the protein structure of the p22(phox) is still uncertain. In this study we use an in silico computational bioinformatic approach to produce a consensus 3-dimensional model of the p22(phox). Based on published protein sequence data of human p22(phox) and by using transmembrane specific protein prediction algorithms, we found that p22(phox) consists of two domains: an N-terminal transmembrane domain (124 a.a.) and a C-terminal cytoplasmic domain (71 a.a.). In its predicted most stable form, p22(phox) contains three transmembrane helices leading to an extracellular N-terminus and an extensive (39 a.a.) extracellular loop between helices 2 and 3. Furthermore, we locate the cytosolic domain phosphorylation site at threonine(147) which literature shows is capable of priming the p22(phox), in order to accept its binding partners. Our results are consistent with the biological characterisation of p22(phox) derived from experiments using specific antibody or genetic manipulation. Our 3-D protein model provides insights into the biological function of p22(phox) and cytochrome b(558), and can be used as tool to investigate the regulatory mechanism of Nox isoforms.
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Several lipoxygenases have been related to inflammation and cardiovascular disease, in particular 5-lipoxygenase and 12/15-lipoxygenase.
“Several lipoxygenases have been related to inflammation and cardiovascular disease, in particular, 5-lipoxygenase and 12/15-lipoxygenase (203, 597, 636).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [636]
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NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology
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- Authors
- Meijles, D. N., Howlin, B. J., & Li, J.-M.
- Affiliations
- University of Surrey (GB)
- Corresponding author
- Howlin, Brendan J.
- Venue
- Computational Biology and Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 39
- Pages
- 6-13
- ISSN
- 1476-9271 (ISSN-L)
- OpenAlex
- W2093909945
- Cited by
- 22
- References
- 28
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 3 · 2016: 3 · 2015: 1 · 2014: 5
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Computational Biology and Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Open Research (University of Surrey) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- p22phox, NADPH oxidase, cytochrome b558, protein structure prediction, transmembrane domain, cytosolic domain, phosphorylation sites, reactive oxygen species, NOX isoforms
- MeSH terms
- Computer Simulation, Humans, Models, Molecular, Software, Protein Structure, Tertiary, NADPH Oxidases
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