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

John P. Donahue, Hareshkumar Patel, Wayne F. Anderson, Jacek Hawiger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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 γ-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 γ chain was determined by x-ray diffraction analysis at a resolution of 2.4 Å. This segment encompasses the recognition site for the integrin α(IIb)β3 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.

Original languageEnglish (US)
Pages (from-to)12178-12182
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number25
DOIs
StatePublished - Dec 6 1994

Keywords

  • cell adhesion
  • chimeric proteins
  • crystallography
  • lysozyme
  • thrombosis

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Three-dimensional structure of the platelet integrin recognition segment of the fibrinogen γ chain obtained by carrier protein-driven crystallization'. Together they form a unique fingerprint.

Cite this