Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598977
Title: Structural studies of the small G protein effector RLIP76 and its interaction with RalB
Author: Fenwick, R. B.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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Abstract:
This dissertation presents structural data relevant to Ral’s role in endocytosis via its interaction with RLIP76. Using in vitro biochemical techniques and NMR spectroscopy the interaction between RalB and the Ral binding domain (RBD) of RLIP76 has been characterised. Binding experiments with the RLIP76 RBD and full length RLIP76 show that Ral binds with a 1 μm affinity for the full length protein, while a higher affinity is expected for the RLIP76 RBD. Binding of ATP to the RLIP76 RBD has also been tested, although results were not able to confirm binding. The solution structures of the free RLIP76 RBD and the complex of this domain with RalB are presented and discussed in the context of the other Ral complexes. The structure of the Ral/RLIP76 RBD complex shows that RLIP76 binds to Ral primarily via the C-terminal helix of the RBD which binds to switch II of the small G protein. The architecture of the complex is such that RLIP76 is in a position to bind D49 of switch I, although the data do not support more extensive contacts with switch I. The structure of the Ral/RLIP76 complex is contrasted with other effector interactions with the small G protein Ral and a review of al helical interactions of effectors with small G proteins has enabled a general binding model for all effectors binding via helical motifs to be established. To understand the role of the Ral/RLIP76 complex in the wider context of endocytosis and RLIP76 signalling, the RhoGAP and Ral binding domains were modelled together. This exploratory modelling of the RhoGAP and Ral binding domains together is presented and used as a basis for the discussion of future work.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.598977  DOI: Not available
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