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Title: Nuclear magnetic resonance methods for obtaining structural and dynamical information for biomolecules of modular composition
Author: Bromek-Burnside, Krystyna Z.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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The complement system is regulated by protein-protein interactions. The binding sites within the regulatory proteins appear to be spread over two-to-four modular units (called CCPs), making it important to understand the relative arrangement of the modules. One- and two-module fragments from membrane cofactor protein (MCP), Vaccinia complement protein (VCP) - a viral mimic known to suppress the activity of complement - and complement receptor type 1 (CR1) were studied. A structural refinement of a fragment containing central CCP modules from VCP (which is composed of four modules) has been performed utilising restraints derived from the residual dipolar couplings (RDCs). The RDCs, cross-validated with the structural content of relaxation rates, provided a proof for structural differences between the NMR and crystal structures. Possible preferred arrangements of the modules have been described. The dynamic description derived from relaxation rates has shown that the link between the two central CCPs of VCP is highly flexible, more so than that between the two terminal ones. An indication of a difference in the level of inter-modular mobility between two CCP module-pairs from CR1 has also been obtained. The sensitivity of structure and stability of CCP modules to the presence of neighbouring modules is discussed. The local motions present at specific residues in each of the studied CCPs from MCP and VCP have been characterised in terms of time-scale and relative amplitude, and a partial description of local motions in the pairs of CCPs from CR1 was also obtained. The residues within the known and proposed binding sites of these proteins share dynamic properties with larger secondary structure elements in which they are located. Most of the residues implicated in binding appear to lie within structured parts of the protein.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available