Low-resolution structure of the complex of human blood platelet factor 4 with heparin determined by small-angle neutron scattering.

ABSTRACT

Small-angle neutron scattering was used to confirm that human platelet factor 4 was a compact tetrameric globular protein of radius of gyration 1.74 nm and indistinguishable from a sphere. The same technique, when applied to the 11 mol/mol complex of platelet factor and heparin of Mr 14000, revealed that the radius of gyration of the particle varied, depending on the relative proportion of 2H2O to H2O in the solvent. Analysis of this variation by the method of Ibel and Stuhrmann (Ibel, K. and Stuhrmann, H.B. (1975) J. Mol. Biol. 93, 255-266) revealed that in the complex the material of greatest neutron-scattering length (the highly sulphated polysaccharide heparin) was furthest from the centre of the particle. This confirms the postulate of Luscombe and Holbrook (Luscombe, M. and Holbrook, J.J. (1983) in Glycoconjugates (Chester, A.M., Heinegård, D., Lundblad, A. and Svensson, S., eds.), pp. 818-819, Secretariat, Lund) that the exact 11 mole ratio of heparin (Mr greater than 10 000) to platelet factor in this stable complex arises from the heparin winding around the outside of a globular protein core.