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Title: Studies on core-swapped fibronectin type III domains
Author: Billings, K. S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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Two homologous fibronectin type III (fnIII) domains, FNfn10 (the tenth fibronectin type III domain of human fibronectin) and TNfn3 (the third fibronectin type III domain of human tenascin), have, essentially, the same backbone structure although they share only ~24% of sequence identity. FNoTNc is a core swapped protein, containing the “outside” (surface and loops) of FNfn10 and the hydrophobic core of TNfn3. Despite the extent of redesign, FNoTNc retains the structure of the parent proteins allowing us to gain insights into which components of each parent protein are responsible for different aspects of its behaviour. Naively, one would expect properties that depend principally on the core to be similar to TNfn3, for example the response to mutation, folding kinetics and sidechain dynamics; while properties determined by difference in the surface and loops, such as backbone dynamics, would be more like FNfn10.  While this is broadly true, it is clear that there are also crosstalk effects between the core and surface. For example, the anomalous response of FNfn10 to mutation is not solely a core property as we had previously suggested. TNoFNc is a core swapped protein, containing the “outside” (surface and loops) of TNfn3 and the hydrophobic core of FNfn10. We infer from our data that TNoFNc has also retained the structure of the parent proteins. TNoFNc is a very unstable protein, which we suggest is due to over-packing of the core. An attempt was made to characterise mutants of TNoFNc, although our investigations were hampered by the presence of a possible impurity which may copurify with the mutant proteins. However, it is clear that the mutants appear to behave very differently to wild-type TNoFNc.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available