The Covalent Structure of Factor XIIIa Crosslinked Fibrinogen Fibrils

Document Type

Article

Publication Date

7-1995

Publisher

Elsevier

Source Publication

Journal of Structural Biology

Source ISSN

1047-8477

Original Item ID

DOI: 10.1006/jsbi.1995.1033

Abstract

When factor XIIIa-mediated crosslinking of fibrin or fibrinogen occurs, reciprocal intermolecular isopeptide bonds form first between paired carboxy terminal γ chain donor-acceptor sites in outer molecular D domains, resulting in γ 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 γ 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 crosslinked 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 -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 γ chain bonds are positioned transversely between strands and are represented by thin filamentous structures bridging the D domains of opposing fibril strand— it follows that the same γ chain crosslink arrangement occurs in fibrin.

Comments

Journal of Structural Biology, Vol. 115, No. 1 (July 1995): 88-101. DOI.

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