s e c t io n 36.3
Functional Properties and Structures of the Hemostatic System Factors (Proteins)
(Also see color figure.) Motif structures within coagulation proteins.
Common motifs are found in the amino terminal regions of the proteinase
precursor molecules. Shown are the kringle motifs and EG F-like motifs
found in the vitamin K-dependent proteins and in plasminogen.
Fibronectin (types I and II) motifs and “apple” motifs (named from their
two-dimensional representations) are also present but not shown. Some
epidermal growth factor-like domains contain /3-hydroxylated Asp
residues. The cartoon structures for the motifs are derived from
three-dimensional structures determined by x-ray crystallography or by
two-dimensional NM R spectroscopy.
either to the surfaces or, in the case of integral pro-
teins (tissue factor and thrombomodulin), spanning the
cell membrane. Cofactor proteins enhance the specificity
of the reactions and increase the rate of activation of
the proteinase precursor. Cofactor proteins are shown as
bar diagrams in Figure 36-6.Cofactor protein activation
occurs by proteolysis of the precursor forms by throm-
bin and factor Xa. Activation of the cofactor proteins
exposes the binding sites for factor Xa and prothrombin
(factor Va) and, by analogy, factor IXa and factor X
(factor Villa). Sites of cleavage are indicated in the
diagrams in the figure. Binding of factors V and Va and
factors VIII and Villa to the phospholipid membrane is
mediated by the C domains; binding to their respective
proteinases and proteinase precursors is mediated by the
A domains.
Proteinase Inhibitors
Proteinase inhibitors (proteins) that circulate in plasma
inactivate the hemostatic system proteinases after they
have “essentially completed” their proteolyses. With two
exceptions, a
-macroglobulin and tissue factor pathway
inhibitor, all of the inhibitors of the procoagulant, an-
ticoagulant, and fibrinolytic proteinases are SERPINS
(Also see color figure.) Cofactor proteins, factor V and factor V III. Factor V and factor V III coagulant (not the von
Willebrand factor carrier of factor V III) contain six distinct structural domains. The two A domains A i and A
at the
N-terminal end of the polypeptide chain are separated from the A
domain by a highly glycosylated B domain. The two
domains are at the C-terminal end of the molecule. The A domain sequences are homologous to the A domains of
ceruloplasmin. Both factor Va and factor V illa act as catalysts in the activation of prothrombin and factor
respectively. In the color version of this figure, activation sites are indicated by green arrows; inactivation sites by red
arrows. In factor Va, complete inactivation requires cleavage of Arg306.
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