Three-dimensional structure of the platelet integrin recognition segment of the fibrinogen gamma chain obtained by carrier protein-driven crystallization.

Donahue JP, Patel H, Anderson WF, Hawiger J
Proc Natl Acad Sci U S A. 1994 91 (25): 12178-82

PMID: 7527555 · PMCID: PMC45400 · DOI:10.1073/pnas.91.25.12178

We have developed a method for crystallizing small functional protein segments so that their three-dimensional structure can be determined by x-ray diffraction analysis. This method consists of linking a small protein segment of unknown tertiary structure to either the amino or carboxyl terminus of a larger carrier protein of known tertiary structure. Crystallization of the small segment is then driven by crystallization of the carrier protein. Using this approach, we have obtained crystals of the human fibrinogen gamma-chain carboxyl-terminal segment linked to the carboxyl terminus of chicken egg white lysozyme. The three-dimensional structure of the carboxyl-terminal segment of the fibrinogen gamma chain was determined by x-ray diffraction analysis at a resolution of 2.4 A. This segment encompasses the recognition site for the integrin alpha IIb beta 3 receptor on activated platelets and for the clumping receptor on pathogenic staphylococci and also bears donor and acceptor sites for factor XIIIa-catalyzed crosslinking of fibrin. Therefore, the structural information derived from our analysis will provide a rational basis for the design of inhibitors of these important functions of fibrinogen. Moreover, carrier protein-driven crystallization will facilitate the determination of the three-dimensional structure of functional segments of other proteins that are, like fibrinogen, difficult to crystallize in toto.

MeSH Terms (21)

Amino Acid Sequence Animals Base Sequence Blood Platelets Chickens Crystallization Fibrin Fibrinogen Humans Hydrogen Bonding Integrins Macromolecular Substances Models, Molecular Molecular Sequence Data Muramidase Oligodeoxyribonucleotides Peptide Fragments Platelet Glycoprotein GPIIb-IIIa Complex Protein Conformation Recombinant Fusion Proteins Restriction Mapping

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