Publisher Summary The production of functional protein units in many cases requires the formation of covalent bonds, and prevalent among these are crosslinks within and between molecules that play a major role in maintaining gross forms of structure and limiting degrees of extensibility. This chapter describes the current knowledge of the distribution, formation, and function of the ɛ-(γ-glutamyl)lysine crosslink, and focuses largely on the crosslink known to be or believed to be formed by the catalytic action of transglutaminases. These enzymes catalyze a calcium-dependent acyl-transfer reaction in which the γ-carboxamide groups of peptide-bound glutamine residues are the acyl donors. Participation of ɛ-amino groups of peptide-bound lysine residues as acyl acceptors yields ɛ-(γ-glutamyl)lysine crosslinks. Although, there is a little doubt that the enzymes described in the chapter are capable of catalyzing crosslink formation, individualities of substrate preference notwithstanding, current data do not prove that this is the biological function of each. The chapter is believed to permit critical evaluation of the information available, suggest areas that hold the greatest opportunity for advances, and will, as a consequence, stimulate further investigations of the synthesis, distribution, and function of the ɛ-(γ-glutamyl)lysine crosslink.

The epsilon-(gamma-glutamyl)lysine crosslink and the catalytic role of transglutaminases.

Fibrinogen is a soluble plasma protein that is converted to polymeric fibrin in response to damage to the vascular system The clotting process is initiated when platelets aggregate at the wound site Their disruption releases biologically active amines and a proteolytic cascade follows which culminates in the conversion of fibrinogen to fibrin The fibrin polymer forms the matrix of the tangle of cellular and molecular substances called the blood clot Atomic-level details are now in hand for many of the interactions that hold fibrin units together, although some aspects have yet to be resolved Of necessity, fibrin clots need to be dismantled when they are no longer needed, an operation largely accomplished by the proteolytic enzyme plasmin Various regulatory phenomena are involved in maintaining the balance between intravascular fluidity and clots that prevent blood loss A variety of hereditary conditions, including mutant fibrinogens, can predispose individuals to either thrombosis or bleeding



Key concepts: 



The underlying fabric of blood clots is a protein polymer called fibrin




Fibrin clots are formed in response to injuries to any part of the vascular system




The conversion of soluble fibrinogen molecules to insoluble fibrin depends on thrombin generated from prothrombin






Keywords:

fibrinogen;
fibrin;
clot stabilisation;
fibrinolysis;
blood clotting;
X-ray structures

Fibrinogen and Fibrin

Human platelets possess an inducible and saturable receptor specific for fibrinogen

2 – Isolation, Physicochemical Characterization, and Carbohydrate-Binding Specificity of Lectins

ACTIN is the most abundant protein in mammalian cells. Cell motility and change in the size and shape of cells depend on the ability of monomers of actin to polymerize to actin filaments. When acti...

The extracellular actin-scavenger system and actin toxicity.

Interaction of lectins with human platelets Effects of platelet stimulation by thrombin and ristocetin

Aggregation of platelets by muscle actin. A multivalent interaction model of platelet aggregation by ADP

Role of surface sialic acid in the interaction of wheat germ agglutinin with human platelets

Characterization and origin of fibrinogen in blood platelets. A review with recent data.

Inhibition of Thrombin-Induced Platelet Aggregation by a Derivative of Wheat Germ Agglutinin. Evidence for a Physiologic Receptor of Thrombin in Human Platelets

Pankaj Ganguly

Papers

Interaction of lectins with human platelets Effects of platelet stimulation by thrombin and ristocetin

Aggregation of platelets by muscle actin. A multivalent interaction model of platelet aggregation by ADP

Role of surface sialic acid in the interaction of wheat germ agglutinin with human platelets

Characterization and origin of fibrinogen in blood platelets. A review with recent data.

Inhibition of Thrombin-Induced Platelet Aggregation by a Derivative of Wheat Germ Agglutinin. Evidence for a Physiologic Receptor of Thrombin in Human Platelets