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

Lasiwa, D.; Kursula, I.

2024-06-16 biochemistry
10.1101/2024.06.16.598887 bioRxiv
Show abstract

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 (AgADF) is reported. AgADF has a conserved ADF/cofilin fold with six central {beta}-strands surrounded by five -helices with a long {beta}-hairpin loop protruding out of the structure. The G and F-actin binding sites of AgADF are conserved, and the structure shows features of potential importance for regulation by membrane binding and redox state. AgADF binds monomeric ATP- and ADP-actin with a high affinity, having a nanomolar Kd, and binds to and effectively destabilizes actin filaments.

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