There is much controversy regarding the conformation of fibrinogen. Several models
have been proposed ranging from an almost linear trinodular arrangement to a globular
conformation. Consequently, it has been suggested that fibrinogen has a flexible structure
where the actual conformation is influenced by its environment - one major factor
being calcium concentration. Although the importance of tightly bound calcium ions
(Kd ∼ luM) to fibrinogen structure is well established, the role of the larger number
of low affinity sites (Kd∼lmM) is still a matter of debate.
We have utilised the techniques of radio-active photoaffinity surface labelling and
chemical cross-linking to probe the molecule's conformation under different conditions.
Studies were carried out in an attempt to provide information on: (1) The relative
locations of the major domains within the fibrinogen molecule (2) The regions of the
chains which are exposed on the surface (3) The dependence of the conformation on
the solvent composition with particular reference to the effect of calcium concentration.
Our results indicate that the central, or E domain of the molecule is partially buried
and that the conformation of fibrinogen is certainly influenced by changes in solvent
composition. Increasing calcium concentration in the millimolar range results in an
increase in the proportion of intermolecular cross-linking, mainly through the [A]α
chains. There have been several reports that the C-terminal regions of the [A]α chains
are in close association, forming a fourth domain within the molecule. Our results
suggest that calcium ions promote the dissociation of this domain.
