Crystal structure of Anopheles gambiae actin depolymerizing factor explains high affinity to monomeric actin

Actin is an intrinsically dynamic protein, the function and state of which are modulated by actin-binding proteins. Actin depolymerizing factors (ADF)/cofilins are ubiquitous actin-binding proteins that accelerate actin turnover. Malaria is an infectious disease caused by parasites of the genus Plasmodium , which belong to the phylum Apicomplexa. The parasites require two hosts to complete their life cycle: the definitive host, or the vector, which is an Anopheles spp. mosquito, and a vertebrate intermediate host, such as humans. Here, the crystal structure of the malaria vector Anopheles gambiae ADF ( Ag ADF) is reported. Ag ADF has a conserved ADF/cofilin fold with six central β-strands surrounded by five α-helices with a long β-hairpin loop protruding out of the structure. The G and F-actin binding sites of Ag ADF are conserved, and the structure shows features of potential importance for regulation by membrane binding and redox state. Ag ADF binds monomeric ATP- and ADP-actin with a high affinity, having a nanomolar K _d , and binds to and effectively destabilizes actin filaments.