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Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin

Nature volume 389, pages 455–462 (1997)Cite this article

An Erratum to this article was published on 20 November 1997

Abstract

In blood coagulation, units of the protein fibrinogen pack together to form a fibrin clot, but a crystal structure for fibrinogen is needed to understand how this is achieved. The structure of a core fragment (fragment D) from human fibrinogen has now been determined to 2.9 Å resolution. The 86K three-chained structure consists of a coiled-coil region and two homologous globular entities oriented at approximately 130 degrees to each other. Additionally, the covalently bound dimer of fragment D, known as ‘double-D’, was isolated from human fibrin, crystallized in the presence of a Gly-Pro-Arg-Pro-amide peptide ligand, which simulates the donor polymerization site, and its structure solved by molecular replacement with the model of fragment D.

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Figure 1: Schematic representation of the three polypeptide chains that compose human fibrinogen fragment D.
Figure 2: a, Ribbon representation of fragment D, showing the region of coiled coils and the globular β and γ domains.
Figure 3: a, Ribbon representation of fragment D, showing the region of coiled coils and the globular β and γ domains.
Figure 4: a, Topology of β-chain (green) and γ-chain (red) C-terminal domains.
Figure 5: a, Topology of β-chain (green) and γ-chain (red) C-terminal domains.
Figure 6: a, Topology of β-chain (green) and γ-chain (red) C-terminal domains.
Figure 7: Multiple alignment of carboxyl domains of fibrinogen β (FBE)- and γ (FGA)-chains from various species (H, human; F, frog; C, chicken; L, lamprey).
Figure 8: a, Electron-density omit map showing peptide ligand Gly-Pro-Arg-Pro-amide bound to γ-chain binding site in double-D as calculated with |Fo| − |Fc| coefficients and phases from the refined model contoured at 2.2σ.
Figure 9: a, Electron-density omit map showing peptide ligand Gly-Pro-Arg-Pro-amide bound to γ-chain binding site in double-D as calculated with |Fo| − |Fc| coefficients and phases from the refined model contoured at 2.2σ.
Figure 10: Four views across the D–D interface as seen from increasing distance.
Figure 11: Four views across the D–D interface as seen from increasing distance.
Figure 12: Four views across the D–D interface as seen from increasing distance.
Figure 13: Four views across the D–D interface as seen from increasing distance.

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Acknowledgements

We thank J. Kraut for the use of his X-ray faciities; M. Sawaya for his time; H.Pelletier for help in establishing the initial crystallization conditions; D. Stuart for assistance; N. Xuong and J. Noel for access to equipment; R. Sweet at the Brookhaven National Laboratory for assistance; G.Walter for encouragement; and M. Riley and L. Veerapandian for technical assistance. This work was supported by an NIH grant and an American Heart Association postdoctoral fellowship to S.J.E.

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  1. Glen Spraggon and Stephen J. Everse: These authors contributed equally to this work.

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  1. Center for Molecular Genetics, University of California, San Diego, La Jolla, 92093-0634, California, USA

    Russell F. Doolittle

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Correspondence to Russell F. Doolittle.

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Spraggon, G., Everse, S. & Doolittle, R. Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin. Nature 389, 455–462 (1997). https://doi.org/10.1038/38947

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