Conformational Analysis of Isolated Domains of Helicobacter pylori CagA
| العنوان: | Conformational Analysis of Isolated Domains of Helicobacter pylori CagA |
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| المؤلفون: | Abolghasem Tohidpour, Terry Kwok, Amanda P. Woon, Hernan Alonso, Anna Roujeinikova, Yumiko Saijo-Hamano |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 11, p e79367 (2013) |
| بيانات النشر: | Public Library of Science, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Scaffold protein, Models, Molecular, Repetitive Sequences, Amino Acid, Protein Denaturation, Science, Molecular Sequence Data, Biology, Intrinsically disordered proteins, Crystallography, X-Ray, Protein Structure, Secondary, Protein–protein interaction, Bacterial Proteins, CagA, Secretion, Amino Acid Sequence, Peptide sequence, Polyproline helix, Antigens, Bacterial, Multidisciplinary, Protein Stability, Temperature, bacterial infections and mycoses, digestive system diseases, Cell biology, Protein Structure, Tertiary, Membrane protein, Biochemistry, Proteolysis, Medicine, Protein Multimerization, Research Article |
| الوصف: | The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variety of host signalling pathways. The recently determined crystal structure of C-terminally-truncated CagA indicated the presence of two domains: the smaller, flexible N-terminal domain and the larger, middle domain. In this study, we have investigated the conformation, oligomeric state and stability of the N-terminal, middle and glutamate-proline-isoleucine-tyrosine-alanine (EPIYA)-repeats domains. All three domains are monomeric, suggesting that the multimerisation of CagA observed in infected cells is likely to be mediated not by CagA itself but by its interacting partners. The middle and the C-terminal domains, but not the N-terminal domain, are capable of refolding spontaneously upon heat denaturation, lending support to the hypothesis that unfolded CagA is threaded C-terminus first through the type IV secretion channel with its N-terminal domain, which likely requires interactions with other domains to refold, being threaded last. Our findings also revealed that the C-terminal EPIYA-repeats domain of CagA exists in an intrinsically disordered premolten globule state with regions in PPII conformation - a feature that is shared by many scaffold proteins that bind multiple protein components of signalling pathways. Taken together, these results provide a deeper understanding of the physicochemical properties of CagA that underpin its complex cellular and oncogenic functions. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c47e1953e785fbd9e1d6c7102ed5153Test http://europepmc.org/articles/PMC3815135Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7c47e1953e785fbd9e1d6c7102ed5153 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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