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Hello. My name is Wolfram Bode.
I'm from the Max-Planck-Institute of Biochemistry in Martinsried, Munich, Germany.
In the following, I'd like to present
some structural features of the coagulation Proteinase Thrombin,
and to show that it is an extremely versatile Janus-Headed Proteinase with
distinct surface regions involved in recognition, binding and catalysis.
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Our blood coagulation system consists of vascular,
cellular and numerous other components.
In this lecture, I will concentrate on the latter.
Coagulation is mainly initiated by this extrinsic pathway an
amplification cascade in which a few trypsinogen like pro enzymes such as factors seven,
nine, 10 and two prothrombin, here represented
by pink spheres, activate each other in successive order,
to the yellow pacman-like actofactors.
This way, any vessel injury induce inflammation of the tissue in factor,
factor seven A complex,
the so-called extrinsic 10Ase triggers the burst like
release of the soluble active alpha Thrombin factor 2A into the vessel lumen.
Thrombin is the main executioner of this cascade,
in that it fulfills
some procoagulant factions that arose such as: conversion of fibrinogen to fibrin,
a cleaving off the two fibrin peptides A and the two fibrin peptides B,
activation of the cross-linking trans glutaminase factor 13,
stimulation of the platelets by cleaving the protease-activated receptors first.
Activation of co-factors five and eight,
which then become brown triangles part of the intrinsic 10ase of the prothrombinase
as well as activation of factor 11,
thus catalyzing further generation of Thrombin,
as well as stimulation of other cells.
But Thrombin can also adopt anticoagulant and antifibronolytic factors,
that it binds in the small capillaries in particular to
the membrane protein Thrombomodulin blocks these programmed properties,
but enables Thrombin to bind and activate protein C, yellow arrows.
Activated protein C in turn is able to degrade these cofactors,
factor 8a and factor 5a, shutting down further Thrombin generation.
All of these activation steps are controlled and regulated by protein inhibitors,
purple triangles, such as Serpins,
antithrombin three and heparin cofactor two, AT3 and HC2.
These inhibitor reactions are assisted by negatively charged carbenoids, particularly heparin.
In most of these factors and complexes about the phospholipid membranes PL mediated by enzymes.
The question therefore arises,
how can a single relatively small protein Thrombin fulfill so many different functions,
interact with so many different substrates, cofactors,
mediators and how are these different functions coordinated?
