Factor XIIIa incorporates thymosin beta4 preferentially into the fibrin(ogen) alphaC-domains.
It was shown recently that tissue transglutaminase and presumably plasma transglutaminase, factor XIIIa, can covalently incorporate into fibrin(ogen) a physiologically active peptide, thymosin beta(4) [(Huff et al. (2002) FASEB J. 16, 691-696]. To clarify the mechanism of this incorporation, we studied the interaction of thymosin beta(4) with fibrinogen, fibrin, and their recombinant fragments, the gamma-module (gamma-chain residues 148-411), and the alphaC-domain (Aalpha-chain residues 221-610) and its truncated variants by immunoblot and ELISA. No significant noncovalent interaction between them was detected in the absence of activated factor XIII, while in its presence thymosin beta(4) was effectively incorporated into fibrin and to a lesser extent into fibrinogen. The incorporation at physiological concentrations of fibrin(ogen) and factor XIII was significant with molar incorporation ratios of thymosin beta(4) to fibrinogen and fibrin of 0.2 and 0.4, respectively. Further experiments revealed that although activated factor XIII incorporates thymosin beta(4) into the isolated gamma-module and alphaC-domain, in fibrin the latter serves as the major incorporation site. This site was further localized to the COOH-terminal portion of the alphaC-domain including residues 392-610.
Biochemistry Department, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855, USA.
Evgeny
E
Makogonenko
Allan L
AL
Goldstein
Paul D
PD
Bishop
Leonid
L
Medved
D000595:Amino Acid Sequence; D026122:Factor XIIIa / Q000378:metabolism*; D005337:Fibrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D017384:Sequence Deletion; D013947:Thymosin / Q000378:metabolism*; D000099201:Thymosin beta(4)
D026122:Factor XIIIa; D005337:Fibrin; D005340:Fibrinogen; D010446:Peptide Fragments; D021122:Protein Subunits; D013947:Thymosin; D000099201:Thymosin beta(4)