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  • Title: The covalent structure of factor XIIIa crosslinked fibrinogen fibrils.
    Author: Mosesson MW, Siebenlist KR, Hainfeld JF, Wall JS.
    Journal: J Struct Biol; 1995; 115(1):88-101. PubMed ID: 7577232.
    Abstract:
    When factor XIIIa-mediated crosslinking of fibrin or fibrinogen occurs, reciprocal intermolecular isopeptide bonds form first between paired carboxy terminal gamma chain donor-acceptor sites in outer molecular D domains, resulting in gamma chain dimers. Their location in the fibrin polymer is not certain, but some evidence suggests they are situated at the outermost ends of the D domains of linearly aligned molecules comprising each strand of double-stranded fibrils ("DD-long"). Other experiments indicate that gamma chain bonds are located between D domains in opposing fibril strands ("transverse"). To distinguish between these possible arrangements, we evaluated the ultrastructure of fibrils and fibers found in factor XIIIa-fibrinogen crosslinking mixtures, based on this reasoning: if DD-long bonding occurs, single-stranded fibrils should result, whereas transverse positioning will result in double-stranded fibrils. Fibrils formed in partially cross-linked fibrinogen solutions consisted of two parallel strands, as discerned visually from scanning transmission electron microscopic images and confirmed by mass per unit length fibril measurements. Neighboring fibrinogen D domains in each fibril strand were aligned end-to-end and were in register with a fibrinogen E domain in the opposite strand, creating a half-staggered molecular arrangement with approximately 22.5-nm periodicity corresponding to half the length of fibrinogen. Ribbon-like fibrinogen fibers, like fibrils, displayed 22.5-nm periodicity, as expected from laterally associated double-stranded fibrils with D domains in register. Taken together, these results indicate that carboxy terminal gamma chain bonds are positioned transversely between strands and are represented by thin filamentous structures bridging the D domains of opposing fibril strands--it follows that the same gamma chain crosslink arrangement occurs in fibrin.
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