We present the 2.6 Å resolution crystal structure of a complex formed between G-actin and gelsolin fragment Met25–Gln160 (G1+). The structure differs from those of other gelsolin domain 1 (G1) complexes in that an additional six amino acid residues from the crucial linker region into gelsolin domain 2 (G2) are visible and are attached securely to the surface of actin. The linker segment extends away from G1 up the face of actin in a direction that infers G2 will bind along the same long-pitch helical strand as the actin bound to G1. This is consistent with a mechanism whereby G2 attaches gelsolin to the side of a filament and then directs G1 toward a position where it would disrupt actin–actin contacts. Alignment of the sequence of the structurally important residues within the G1–G2 linker with those of WH2 (WASp homology domain 2) domain protein family members (e.g. WASp (Wiscott–Aldridge syndrome protein) and thymosin β4) suggests that the opposing activities of filament assembly and disassembly may exploit a common patch on the surface of actin.
