Work

Transglutaminase-catalyzed crosslinking of the Aα and γ constituent chains in fibrinogen

Year: 2000

Type: article

Abstract: Studies on transglutaminases usually focus on the polymerization of protein substrates by intermolecular N(epsilon)(gamma-glutamyl)lysine bridges, without considering the possibility that the monomeric protein units, themselves, could also become crosslinked internally. Both types of crosslinks are produced in the reaction of fibrinogen with red cell transglutaminase. We isolated the transglutaminase-modified, mostly monomeric form (92-96%) of fibrinogen with a N(epsilon)(gamma-glutamyl)lysine content of approximately 1.6 moles/mole of fibrinogen. The preparation was fully clottable by thrombin, but the rates of release of fibrinopeptides and clotting times were delayed compared with control. Hybrid Aalpha.gamma type of crosslinking, the hallmark of the reaction of the transglutaminase with fibrinogen, occurred by bridging the Aalpha(408-421) chain segment of the protein to that of gamma(392-406). Rotary shadowed electron microscope images showed many monomers to be bent, and the crosslinks seemed to bind the otherwise flexible alphaC domain closer to the backbone of fibrinogen.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.97.1.44

Authors: S. N. Prasanna Murthy, James H. Wilson, Thomas J. Lukas, Yuri Veklich, John W. Weisel, Laszlo Lorand

Institutions: Northwestern University, University of Pennsylvania

Language: English

Topic: Blood properties and coagulation

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences