UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Unravelling the structure of glycosylated and deglycosylated immunoglobulin G antibodies

Spiteri, Valentina Arancia; (2021) Unravelling the structure of glycosylated and deglycosylated immunoglobulin G antibodies. Doctoral thesis (Ph.D), UCL (University College London).

[thumbnail of Spiteri_10132434_Thesis_redacted.pdf] Text
Spiteri_10132434_Thesis_redacted.pdf
Access restricted to UCL open access staff until 1 September 2022.

Download (39MB)

Abstract

Immunoglobulin G (IgG) is composed of four IgG subclasses, IgG1, IgG2, IgG3 and IgG4, which although differ in function and structure, owing to variability in hinge length, all have a conserved N-linked glycan attached in the Fc region. However, the role of this glycan on the structure, stability and function of these IgG molecules is not fully understood. The focus of this thesis is to investigate the role of the Fc-glycan in respect to IgG1, IgG3 and IgG4 by using a multidisciplinary approach to study both their glycosylated and deglycosylated forms. Primarily by probing the full-length solution structure using small angle X- ray and neutron scattering, as well as analytical ultracentrifugation. Following this extensive computational modelling methods and analysis were used to extract the theoretical models which best fit the solution structure data in order to unpick the role of this glycan. Several studies have investigated the role of the IgG1 Fc-glycan using different structural methods, however, most of these studies investigated the Fc region of IgG rather than the full-length antibody, composed of Fabs, hinge and Fc. In this thesis all experiments are conducted on full-length IgGs, presenting a complete understanding on the effect of the Fc-glycan on the entirety of the IgG structure. Studies of IgG1 and IgG4 indicate that the Fc-glycan plays a role in restricting the flexibility of the Fc. This restriction is less obvious in IgG3; this may be owing to the molecule’s elongated hinge. Of the three antibodies studied, IgG3 has the longest hinge region, composed of 62 amino acids. This long hinge has historically made it difficult to study using other structural techniques, such as X- ray crystallography and NMR, therefore the study of the IgG3 solution structure presented herein is the most complete to date and provides insight into the dynamics of the hinge region.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Unravelling the structure of glycosylated and deglycosylated immunoglobulin G antibodies
Event: Univeristy College London
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
Keywords: IgG, Antiibodies, Immunoglobulin G, IgG1, IgG3, IgG4, glycosylation, SAXS, SANS, small angle scattering
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10132434
Downloads since deposit
3Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item