Cross-linked γ-chains in fibrin fibrils bridge transversely between strands:: no

Factor (F)XIIIa introduces a pair of E-amino-(γ-glutamyl)lysine isopeptide bridges between the C-terminal γ-chains of two fibrin molecules, involving a donor γ406 lysine of one chain and a glutamine acceptor at γ398/399 of another. Conflicting evidence on whether these cross-links occur between molecules that are interacting in a longitudinal or transverse manner will be reviewed. Longitudinal cross-links would occur across the end-to-end junction of two γ -chains within one strand of a protofibril, while transverse cross-links would require long γ-chain extensions from near the ends of two half-staggered molecules to the midpoint between the ends and central region of the molecule (indicated by arrowheads in Fig. 1). This controversy is a significant issue because the topology of these cross-links has important consequences for our understanding of clot structure, stability, and susceptibility to fibrinolysis. I will summarize relevant data from X-ray crystallography, the products of lysis, electron microscopy, and studies of the interactions between fibrin and fibrinogen/fragment D. © 2004 International Society on Thrombosis and Haemostasis.