Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491284
Title: Structural studies on CD55 and its human ligands
Author: Abbott, Rachel J. M.
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2008
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Abstract:
Human CD55 is a 70kDa protein found on the surface of serum-exposed cells: It has long been recognised as a regulator of the complement system, protecting self-cells by accelerating the decay of the C3 and C5 convertases. Much more recently CD55 has also been identified as a co-stimulator of T cells. I have used a wide range of biophysical techniques to study CD55 and its interaction with two human ligands, Bb and CD97. The interaction of CD55 with Bb has been investigated in the hope of contributing to the understanding of how CD55 accelerates decay of the alternative pathway C3 convertase (C3bBb). Surface plasmon resonance experiments have confirmed that CD55 binds to the vWF-A domain of Bb in the presence of Mg2 + and the KD of this interaction has been measured as 2.2JlM. Electron paramagnetic resonance has been used to obtain experimentally-derived distance restraints in order to model the complex between CD55 and the Bb vWF-A domain. CD55 has previously been shown to co-regulate T cell activity via its interaction with CD97, the archetypal member of the EGF-TM7 family of proteins. Using X-ray crystallography, I have determined the structure of EMR2, a very close homologue of CD97. Nuclear magnetic resonance-based chemical shift mapping of the CD55EMR2 interaction has allowed me to generate a model for the CD55-CD97 complex. The structure of this complex reveals that the T cell and complement regulatory activities of CD55 occur on opposite faces of the molecule. This suggests that CD55 is capable of promoting an adaptive immune response while simultaneously protecting self-cells from the innate immune system.
Supervisor: Not available Sponsor: Not available
Qualification Name: University of Oxford, 2008 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.491284  DOI: Not available
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