Crystal structure of a 30 kDA C-terminal fragment from the γ chain of human fibrinogen

Vivien C. Yee, Kathleen P. Pratt, Hélène C.F. Côté, Isolde Le Trong, Dominic W. Chung, Earl W. Davie, Ronald E. Stenkamp, David C. Teller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

229 Scopus citations


Background: Blood coagulation occurs by a cascade of zymogen activation resulting from minor proteolysis. The final stage of coagulation involves thrombin generation and limited proteolysis of fibrinogen to give spontaneously polymerizing fibrin. The resulting fibrin network is covalently crosslinked by factor XIIIa to yield a stable blood clot. Fibrinogen is a 340 kDa glycoprotein composed of six polypeptide chains, (αβγ)2, held together by 29 disulfide bonds. The globular C terminus of the γ chain contains a fibrin-polymerization surface, the principal factor XIIIa crosslinking site, the platelet receptor recognition site, and a calcium-binding site. Structural information on this domain should thus prove helpful in understanding clot formation. Results: The X-ray crystallographic structure of the 30 kDa globular C terminus of the γ chain of human fibrinogen has been determined in one crystal form using multiple isomorphous replacement methods. The refined coordinates were used to solve the structure in two more crystal forms by molecular replacement; the crystal structures have been refined against diffraction data to either 2.5 Å or 2.1 Å resolution. Three domains were identified in the structure, including a C-terminal fibrin polymerization domain (P), which contains a single calcium-binding site and a deep binding pocket that provides the polymerization surface. The overall structure has a pronounced dipole moment, and the C-terminal residues appear highly flexible. Conclusions: The polymerization domain in the γ chain is the most variable among a family of fibrinogen-related proteins and contains many acidic residues. These residues contribute to the molecular dipole moment in the structure, which may allow electrostatic steering to guide the alignment of fibrin monomers during the polymerization process. The flexibility of the C terminal residues, which contain one of the factor XIIIa crosslinking sites and the platelet receptor recognition site, may be important in the function of this domain.

Original languageEnglish
Pages (from-to)125-138
Number of pages14
Issue number1
StatePublished - 15 Jan 1997
Externally publishedYes


  • blood coagulation
  • calcium binding
  • factor XIIIa crosslinking
  • fibrin polymerization
  • fibrinogen


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