CRYSTAL-STRUCTURE OF RECOMBINANT HUMAN PLATELET FACTOR-4

The crystal structure of human platelet factor 4 (PF4) has been solved to a resolution of 2.4 Angstrom by molecular replacement and refined to an R-factor of 24.1%. The structure consists of four polypeptide ch ains which form a tetrameric unit. N-terminal residues, previously def ined as a random coil or extended loop region, form antiparallel beta- sheet-like structures that form noncovalent associations between dimer s. These antiparallel beta-sheet-like structures are positioned latera l to the beta-bilayer motif and stabilize the tetrameric unit. A posit ively charged ring of lysine and arginine side chains encircles the PF 4 tetramer sphere, presenting multiple potential sites and orientation s for heparin binding. The electrostatic interactions of multiply char ged amino acid side chains and hydrogen bonding interactions at the AB /CD dimer interface serve to stabilize the tetrameric structure furthe r.