THE REPEATING SEGMENTS OF THE F-ACTIN CROSS-LINKING GELATION FACTOR (ABP-120) HAVE AN IMMUNOGLOBULIN-LIKE FOLD

The 120,000 M(r) gelation factor and a-actinin are among the most abun dant F-actin cross-linking proteins in Dictyostelium discoideum. Both molecules are rod-shaped homodimers. Each monomer chain is comprised o f an actin-binding domain and a rod domain. The rod domain of the gela tion factor consists of six 100-residue repetitive segments with high internal homology. We have now determined the three-dimensional struct ure of segment 4 of the rod domain of the gelation factor from D. disc oideum using NMR spectroscopy. The segment consists of seven beta-shee ts arranged in an immunoglobulin-like (Ig) fold. This is completely di fferent from the a-actinin rod domain which consists of four spectrin- like alpha-helical segments. The gelation factor is the first example of an Ig-fold found in an actin-binding protein. Two highly homologous actin-binding proteins from human with similar sequences to the gelat ion factor, filamin and a 280,000 M(r) actin-binding protein (ABP-280) , share conserved residues that form the core of the gelation factor r epetitive segment structure. Thus, the segment 4 structure should be c ommon to this subfamily of the spectrin superfamily. The structure of segment 4 together with previously published electron microscopy data, provide an explanation for the dimerization of the whole gelation fac tor molecule.