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Probing the interactions between U24 from HHV-6B and hNedd4L WW and Fyn-SH3 domains Pi, Keng-Shuo
Abstract
Multiple sclerosis (MS) is neurological inflammatory disease in the central nervous system (CNS) that affects every 1 in 400 people in Canada. Although it was first characterized over a century ago, the cause of MS remains elusive, as does consequently a cure. Many factors have been identified as possible triggers, including viruses such as the highly prevalent and latent human herpes virus type 6 (HHV-6) – a member of the Roseolovirus family. There are two variants of this virus, namely HHV-6A and -6B, and the protein U24, encoded in both forms, has been found to be implicated in multiple sclerosis. This thesis describes the study of the binding interaction of U24 from HHV-6B (U24-6B) and two protein binding partners: the WW3* domain from human Neural precursor cell expressed developmentally down-regulated protein 4 like (hNedd4L-WW3*) and the SH3 domain from Fyn tyrosine kinase (Fyn-SH3). These interactions help to further define U24s’ function. Previous studies have suggested that U24 from HHV-6A (U24-6A) and HHV-7 are involved in endocytic recycling of key T-cell receptors, a process mediated by WW domains. Moreover, earlier work has shown that U24-6A may be involved in triggering an autoimmune reaction in MS, through its molecular mimicry of myelin basic protein (MBP), a protein that interacts with Fyn-SH3. None of this previous research investigated whether U24-6B, which is highly homologous to U24-6A, functions in the same way. Hence this thesis aims to fill in this knowledge gap. The interaction between U24-6B and hNedd4L-WW3* was investigated using isothermal titration calorimetry (ITC). The effect of the post-translational modification of phosphorylation at residue Thr6 was also probed. The interaction between U24-6B and Fyn-SH3 was characterized using nuclear magnetic resonance (NMR) spectroscopy. Both these studies shed further insight into the function of U24 from Roseolovirus and its potential role in MS.
Item Metadata
Title |
Probing the interactions between U24 from HHV-6B and hNedd4L WW and Fyn-SH3 domains
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Creator | |
Supervisor | |
Publisher |
University of British Columbia
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Date Issued |
2021
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Description |
Multiple sclerosis (MS) is neurological inflammatory disease in the central nervous system (CNS) that affects every 1 in 400 people in Canada. Although it was first characterized over a century ago, the cause of MS remains elusive, as does consequently a cure. Many factors have been identified as possible triggers, including viruses such as the highly prevalent and latent human herpes virus type 6 (HHV-6) – a member of the Roseolovirus family. There are two variants of this virus, namely HHV-6A and -6B, and the protein U24, encoded in both forms, has been found to be implicated in multiple sclerosis.
This thesis describes the study of the binding interaction of U24 from HHV-6B (U24-6B) and two protein binding partners: the WW3* domain from human Neural precursor cell expressed developmentally down-regulated protein 4 like (hNedd4L-WW3*) and the SH3 domain from Fyn tyrosine kinase (Fyn-SH3). These interactions help to further define U24s’ function. Previous studies have suggested that U24 from HHV-6A (U24-6A) and HHV-7 are involved in endocytic recycling of key T-cell receptors, a process mediated by WW domains. Moreover, earlier work has shown that U24-6A may be involved in triggering an autoimmune reaction in MS, through its molecular mimicry of myelin basic protein (MBP), a protein that interacts with Fyn-SH3. None of this previous research investigated whether U24-6B, which is highly homologous to U24-6A, functions in the same way.
Hence this thesis aims to fill in this knowledge gap. The interaction between U24-6B and hNedd4L-WW3* was investigated using isothermal titration calorimetry (ITC). The effect of the post-translational modification of phosphorylation at residue Thr6 was also probed. The interaction between U24-6B and Fyn-SH3 was characterized using nuclear magnetic resonance (NMR) spectroscopy. Both these studies shed further insight into the function of U24 from Roseolovirus and its potential role in MS.
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Genre | |
Type | |
Language |
eng
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Date Available |
2022-01-10
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0406238
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2022-05
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International