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Title: Structural biology of prohibitins and annexin B1
Author: Winter, Anja
ISNI:       0000 0004 2728 615X
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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This thesis deals with the structural biology of two integral membrane proteins, prohibitin1 and prohibitin 2, and the membrane-associated protein Annexin B1. The biophysical properties of the proteins were characterised and their interaction with different ligands was investigated. Furthermore, crystallisation trials were undertaken in both projects. Prohibitins are members of the evolutionary well-conserved SPFH (stomatin/prohibitin/flotillin/HflK/C) super-family and exert important cellular functions such as cell-cycle control, tumour suppression and regulation of protein turnover in mitochondria. In vivo, prohibitins consist of two proteins, prohibitin 1 and prohibitin 2, that form a transmembrane complex in the inner mitochondrial membrane. The complex of full-length prohibitins 1 and prohibitin 2 could be refolded successfully but only generation of truncation mutants enabled characterisation of the protein complex using spectroscopic methods. Homology modelling of the PHB domains of prohibitin 1 and 2 allowed insights into their three-dimensional structures, their dimer formation and the interactions with target proteins and melanogenin. Furthermore, an interaction with the inter-membrane space region of mitochondrial m- AAA-protease was proposed. The intermembrane space region of m-AAA-protease from E. coli was investigated using spectroscopic methods and subjected to crystallisation trials. Annexin B1 belongs to the well-conserved family of annexins that are versatile adapter and regulator proteins in membrane-associated processes. Similar to other annexins, annexin B1 was found to bind to liposomes and heparin in a calcium-dependent fashion. Interestingly, its liposome binding behaviour is reminiscent of plant annexins suggesting the presence of a calcium-independent binding mode, whereas its lectin property is a shared feature with mammalian annexins. Annexin B1 shows Redoxdependent oligomer formation in solution.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biological Sciences