Molten globule monomer to condensed dimer: role of disulfide bonds in platelet factor-4 folding and subunit association.

Platelet factor 4 (PF4) exhibits high affinity for heparin and exists as a tetramer in solution under physiologic conditions. Reduction of the two disulfide bridges in PF4 increases the protein's dissociation constant for heparin approximately 20-fold and shifts the highest apparent aggregation state from tetramer to dimer as evidenced by gel filtration, chemical cross-linking, and 1 H-NMR studies. 1 H-NMR spectra of reduced PF4 monomers generally show narrower, less dispersed, upfield-shifted NH and αH resonances, suggesting the presence of an unfolded monomer state