Conformational studies of fibrinogen and its derivatives
MetadataShow full item record
There is much controversy regarding the conformation of fibrinogen. Several models have been proposed ranging from a trinodular arrangement to a globular conformation. It has also been suggested that fibrinogen has a flexible structure where the shape of the molecule is influenced by its environment, one major factor being calcium concentration, In addition, although the importance of tightly bound calcium ions (kd 1M) to the fibrinogen molecule is well established, the role of the larger number of low affinity sites (kd 1mM) is still a matter of some debate. In this study, the two techniques of photosensitized radioactive surface labelling and photosensitized cross-linking were selected for development and assessment. This was done with a view to examining the conformation of fibrinogen in its native state and under different solvent conditions, with particular reference to the influence of calcium. The two techniques have been shown to have definite applications in their use as probes into the conformation of fibrinogen. Results derived using these methods support the view put forward by various authors that fibrinogen is a dynamic molecule having a flexible conformation and that the conformation adopted is dependent on solvent composition. Calcium concentration in the millimolar range is particularly significant and consequently so is the saturation of the low affinity binding sites which may well have a regulatory function. Experimentally two extreme conformations have been demonstrated, - a closed, compact structure at low calcium concentrations compared to a more open one at higher calcium concentrations. More importantly, the techniques used also show the subtle changes which occur within the molecule as the calcium concentration is raised, changes which may be more significant physiologically. The most important of these are the effect of calcium on the C-terminal parts of the Aa-chains and the D domains of the molecule.
Thesis, PhD Doctor of Philosophy
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.