The Wriggers Model
The model above was obtained using a directed modeling approach to dock cofilin onto actin basd on the co-crystal structure of gelsolin (has a homologous actin binding domain to cofilin) with actin. This model could not agree more with our two-hybrid data. We found that act1-103 (alters amino acids 334, 335, and 336), act1-106 (alters amino acids 290, 291, and 292) and act1-126 (alters amino acids 326 and 328) could not bind to actin in a two-hybrid assay. As can be seen above, the Wriggers model predicts close contact between cofilin and actin residues 326 and 328 (act1-126), actin residues 291 and 292 (act1-106) and actin residue 334 (act1-103). Note that both our and the Wriggers models likely reflect G-actin binding but Dr. Amy McGough believes that both F- and G-actin binding will share contact sites (personal communication).