Structural determinations of four helical vertebrate cytokines that stimulate the production of blood cells

Adachi, Motoyasu; Meguro, Mizue*; Maekawa, Shun*; Okazaki, Nobuo*; Beppu, Miho*; Nagasawa, Kazumichi*; Hirano, Ayumi*; Tamada, Taro; Kato, Takashi; Kuroki, Ryota

The crystal structures of human EPO and human TPO have been determined both as a receptor bound form and a monoclonal antibody bound form, but isolated structures have not been determined. To determine how much structural and functional differences in hematopoietic cell growth factors exist, we are investigating structure and function of EPO and TPO homologues derived from other vertebrates such as amphibian and fish. Recently, we succeeded in preparations of recombinant EPOs from Xenopus laevis (xl-EPO) and Oryzias latipes (ol-EPO) using E. coli expression and Brevibacillus secretion systems, respectively, and both EPOs were successfully crystallized. The structure determinations of xl-EPO and ol-EPO will contribute to further understanding of the structure-function relationships of EPO including the structural change upon receptor binding.