Transglutaminase-Catalyzed Crosslinking of the Aα and γ Constituent Chains in Fibrinogen
Studies on transglutaminases usually focus on the polymerization of protein substrates by intermolecular Nε(γ -glutamyl) lysine bridges, without considering the possibility that the monomeric protein units, themselves, could also become crosslinked internally. Both types of crosslinks are produced i...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 1; pp. 44 - 48 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
National Academy of Sciences of the United States of America
04.01.2000
National Acad Sciences The National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Studies on transglutaminases usually focus on the polymerization of protein substrates by intermolecular Nε(γ -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 Nε(γ -glutamyl) lysine content of ≈ 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 Aα · γ type of crosslinking, the hallmark of the reaction of the transglutaminase with fibrinogen, occurred by bridging the Aα (408-421) chain segment of the protein to that of γ (392-406). Rotary shadowed electron microscope images showed many monomers to be bent, and the crosslinks seemed to bind the otherwise flexible α C domain closer to the backbone of fibrinogen. |
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Bibliography: | To whom reprint requests should be addressed at: Department of Cell and Molecular Biology, Northwestern University Medical School, Searle 4–555, 303 East Chicago Avenue, Chicago, IL 60611-3008. E-mail: l-lorand@nwu.edu. Contributed by Laszlo Lorand |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.97.1.44 |