Figure 1.

Crystal structure of the PF4/heparin complex and formation of ultralarge complexes. (A) Overall structure of the PF4/fondaparinux complex. Fondaparinux makes contact with a single PF4 tetramer in the groove among the monomers on one side of the asymmetric tetramer. Monomers A, B, C, and D in one PF4 tetramer are colored in green, cyan, magenta, and yellow, respectively. (B) Analysis of crystal lattice reveals a molecular pathway for the formation of antigenic complexes. A fragment of heparin first binds within the groove of one PF4 tetramer (limon, left); binding of the first PF4 tetramer imparts a local linearized structure on heparin, which enhances the binding of a second tetramer (pale green, middle); and progression of this process eventuates in the formation of ultralarge antigenic complexes (right). Reprinted from Cai et al⁵ with permission.