- Title
- Modelling the structure and interactions of leukocyte integrins
- Creator
- Dawson, Kyle-Richard
- Subject
- Proteins -- Structure
- Subject
- Molecular immunology Biochemistry
- Date Issued
- 2019
- Date
- 2019
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- http://hdl.handle.net/10948/39392
- Identifier
- vital:35239
- Description
- Heterodimeric transmembrane protein structure is complex and insufficient structural information exists, concerning leukocyte integrin proteins. To determine protein structure, homology modelling was conducted and modelling software was evaluated. Leukocyte integrin homologs were obtained from the PDB and models were generated using online servers and MODELLER. Template homologs were fewer in number and of lower quality in comparison to monomeric extracellular proteins. Models were docked using ClusPro, HADDOCK2.2 and AutoDock vina. Models were evaluated using PROSA, Verify-3D and PROSESS. Higher quality models were generated when using MODELLER to separately model monomeric subunits in three defined domain regions (extracellular, transmembrane and cytoplasmic). Template selection concerning these proteins is critical as an intricate relationship exists between model quality, template quality, template quantity, template resolution, target-template identity and template sequence coverage. Docking monomeric subunits was challenging when using ClusPro and the best ligand docking procedures were completed using AutoDock vina. PROSESS provided the most accurate evaluation of protein models, in comparison to PROSA and Verify-3D. These results indicate that although homology modelling is a powerful tool there is much room for improvement. Experimentally obtained templates should be expanded upon within the PDB and energy functions should cater for both monomeric and transmembrane heterodimeric proteins. Leukocyte integrins appear to adopt a closed conformation, which may still facilitate LDV ligand association within the α/β interface. The α3β1 integrin may interact with laminin-5 through the ELV sequence within the G-domain of the α laminin subunit
- Format
- xi, 119 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
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NMU School of BioMolecular and Chemical Sciences
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Kyle-Richard Dawson.pdf | 6 MB | Adobe Acrobat PDF | View Details Download |