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Structure of the fibrinogen γ-chain integrin binding and factor XIIIa cross-linking sites obtained through carrier protein driven crystallization

Published online by Cambridge University Press:  01 December 1999

SCOTT WARE ,
JOHN P. DONAHUE ,
JACEK HAWIGER  and
WAYNE F. ANDERSON
SCOTT WARE
Affiliation:
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611
JOHN P. DONAHUE
Affiliation:
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 Present address: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
JACEK HAWIGER
Affiliation:
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
WAYNE F. ANDERSON
Affiliation:
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611
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Abstract

The human fibrinogen γ-chain C-terminal segment functions as the platelet integrin binding site as well as the Factor XIIIa cross-linking substrate and thus plays an important role in blood clot formation and stabilization. The three-dimensional structure of this segment has been determined using carrier protein driven crystallization. The C-terminal segment, γ-(398–411), was attached to a linker sequence at the C-terminus of glutathione S-transferase and the structure of this fusion protein determined at 1.8 Å resolution. Functional studies of the chimeric protein demonstrate that the fibrinogen sequence in the presence of the carrier protein retains its specific functions as ligand for platelet integrin αIIb β3 (gpIIb/IIIa) and as a cross-linking substrate for Factor XIIIa. The structure obtained for the fibrinogen γ-chain segment is not affected by crystal packing and can provide the missing links to the recently reported model of cross-linked fibrin.

Keywords

crystallizationcrystal structurefibrinogenfusion proteinglutathione S-transferaseintegrin
Type
Research Article
Information
Protein Science , Volume 8 , Issue 12 , December 1999 , pp. 2663 - 2671
Copyright
© 1999 The Protein Society

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