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Effects of IRAK-4 phosphomimetics on the Myddosome assembly
Dissertation (MSc)--University of Pretoria, 2018.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2019
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| _version_ | 1867613670798786560 |
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| access_status_str | Open Access |
| author2 | Motshwene, Precious G. |
| author_browse | Motshwene, Precious G. |
| author_facet | Motshwene, Precious G. |
| collection | Thesis |
| dc_rights_str_mv | © 2019 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc)--University of Pretoria, 2018. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/72700 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:39:50.639Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2019 |
| publishDateRange | 2019 |
| publishDateSort | 2019 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/72700 Effects of IRAK-4 phosphomimetics on the Myddosome assembly Motshwene, Precious G. u10667092@tuks.co.za Thipa, David Difateng UCTD Dissertation (MSc)--University of Pretoria, 2018. MyD88 and IRAK-4 are two intracellular proteins that are involved in innate immunity. They form an oligomeric complex known as the Myddosome when a Toll-like receptor is activated upon ligand binding. This complex forms part of post-receptor signalling and is assembled by the interaction of death domains of both proteins. The regulatory mechanisms of assembly and dissociation of the Myddosome are not yet fully understood. One possible mechanism is that autophosphorylation regulates the assembly of the Myddosome. IRAK-4 is a serine/threonine kinase that phosphorylates another kinase, IRAK-1 during TLR signaling. In addition to phosphorylating IRAK-1, it also phosphorylates itself, a process known as autophosphorylation. Its autophosphorylation is an intramolecular event that starts in the kinase loop and extends to its death domain. It is reported that two autophosphorylation sites namely serine 8 and threonine 62 were mapped to its death domain. We substituted these two amino acids with aspartic acid to create phosphomimetics. The mutant phosphomimetics were expressed in E. coli cells and thereafter purified with the aim of determining if they will form the Myddosome when mixed with MyD88 death domain. Wild type and phosphomimetic complexes were formed and characterized using size exclusion chromatography, dynamic scattering and analytical ultracentrifugation. Our results showed that phosphomimetic mutants were able to form an oligomeric complex similar in size to the Myddosome. This result was contrary to what has been reported in literature. We therefore concluded that phosphomimetics were not ideal replacements for phosphorylation. Microbiology and Plant Pathology MSc Unrestricted 2019-12-13T08:07:40Z 2019-12-13T08:07:40Z 2019/09/05 2018 Dissertation Thipa, DD 2018, Effects of IRAK-4 phosphomimetics on the Myddosome assembly, MSc Disertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/72700> S2019 http://hdl.handle.net/2263/72700 en © 2019 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Effects of IRAK-4 phosphomimetics on the Myddosome assembly |
| title | Effects of IRAK-4 phosphomimetics on the Myddosome assembly |
| title_full | Effects of IRAK-4 phosphomimetics on the Myddosome assembly |
| title_fullStr | Effects of IRAK-4 phosphomimetics on the Myddosome assembly |
| title_full_unstemmed | Effects of IRAK-4 phosphomimetics on the Myddosome assembly |
| title_short | Effects of IRAK-4 phosphomimetics on the Myddosome assembly |
| title_sort | effects of irak 4 phosphomimetics on the myddosome assembly |
| topic | UCTD |
| url | http://hdl.handle.net/2263/72700 |