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The plasmin–antiplasmin system: structural and functional aspects

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Abstract

The plasmin–antiplasmin system plays a key role in blood coagulation and fibrinolysis. Plasmin and α2-antiplasmin are primarily responsible for a controlled and regulated dissolution of the fibrin polymers into soluble fragments. However, besides plasmin(ogen) and α2-antiplasmin the system contains a series of specific activators and inhibitors. The main physiological activators of plasminogen are tissue-type plasminogen activator, which is mainly involved in the dissolution of the fibrin polymers by plasmin, and urokinase-type plasminogen activator, which is primarily responsible for the generation of plasmin activity in the intercellular space. Both activators are multidomain serine proteases. Besides the main physiological inhibitor α2-antiplasmin, the plasmin–antiplasmin system is also regulated by the general protease inhibitor α2-macroglobulin, a member of the protease inhibitor I39 family. The activity of the plasminogen activators is primarily regulated by the plasminogen activator inhibitors 1 and 2, members of the serine protease inhibitor superfamily.

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Abbreviations

A2PI:

α2-Antiplasmin, α2-Plasmin inhibitor

CHO:

Carbohydrate

EGF-like:

Epidermal growth factor-like

FN1:

Fibronectin type I

K:

Kringle

LBS:

Lysine binding site

LMW:

Low molecular weight

α2M:

α2-Macroglobulin

NTP:

N-terminal peptide of Pgn

PAI-1, -2:

Plasminogen activator inhibitor 1, 2

Pgn:

Plasminogen

Plm:

Plasmin

RCL:

Reactive centre loop

Serpin:

Serine protease inhibitor

tPA:

Tissue-type plasminogen activator

uPA:

Urokinase-type plasminogen activator

uPAR:

Urokinase-type plasminogen activator receptor

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  1. Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland

    Johann Schaller & Simon S. Gerber

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The recommended names in the UniProt Knowledgebase (SwissProt and TrEMBL) were used. The protein structures are based on the coordinates deposited in the Protein Data Bank (PDB) and were visualized as well as rendered using the software PyMOL. If not stated otherwise, the standard rainbow colour representation was used.

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Schaller, J., Gerber, S.S. The plasmin–antiplasmin system: structural and functional aspects. Cell. Mol. Life Sci. 68, 785–801 (2011). https://doi.org/10.1007/s00018-010-0566-5

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