Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.724892
Title: Towards a structural model of adherent knobs on the surface of Plasmodium falciparum infected erythrocytes
Author: Cutts, Erin Eloise
ISNI:       0000 0004 6421 4155
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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Abstract:
The Plasmodium falciparum proteome is enriched in intrinsically disordered proteins, three of which are directly linked to malaria severity; P. falciparum Erythrocyte Membrane Protein 1 (Pf EMP1), Knob-associated Histidine-rich Protein (KAHRP) and Plasmodium He- lical Interdispersed Sub-telomeric family member (PHIST) PFE1605w. Pf EMP1, KAHRP and PFE1605w all localised to protrusions (knobs) on the P. falciparum-infected erythrocyte surface, which enable pathogenic cytoadherence of infected erythrocytes to uninfected erythrocytes and endothelial cells. In this thesis, I have employed a combination of biophysical and computational methods to characterize the interactions of Pf EMP1 and KAHRP with host erythrocyte spectrin, and of Pf EMP1 with two PHIST family proteins, PFI1780w and PFE1605w. These interactions are likely to assist knob formation and, thus, promote cytoadherence. I derived atomistic structural models of complexes formed between the PHIST domain of PFI1780w and the disordered C-terminal region of the cytosolic domain of Pf EMP1, of the folded core of the Pf EMP1 cytosolic domain and domain 17 of the host erythrocyte a spectrin, and between the KAHRP 5' sequence repeat and domains 10-14 of β spectrin. Combining these structural models with previous electron microscopy information allows us to propose a detailed model as to how knobs form and how Pf EMP1, KAHRP, PFE1605w, and other possible factors could locate therein.
Supervisor: Vakonakis, Ioannis ; Sansom, Mark Sponsor: Wellcome Trust ; Clarendon Fund
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.724892  DOI: Not available
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