[3P-1] Poster 3 (3P-01ー3P-47)

[3P-13] Molecular evolutionary analysis of phosphatidylinositol 5-phosphate 4-kinaseβ (PI5P4Kβ) based on X-ray crystal structure

^○Lisa Nagase¹, Ayaka Harada¹, Miki Senda¹, Koh Takeuchi², Atsuo Sasaki³, So Nakagawa⁴, Toshiya Senda¹ (1.SBRC, IMSS, KEK, 2.Mol. Profiling Res. Ctr. for Drug Discovery, AIST, 3.Dept. of Internal Med., Univ. of Cincinnati Coll. of Med, 4.Dept. of Mol. Life Sci., Tokai Univ. Sch. of Med.)

GTP plays an important role in maintaining the cellular activity. In multicellular organisms, cellular activity is properly controlled in each organ. Therefore, regulation of the GTP activity is essential for multicellular organisms. In 2016, our group reported that human PI5P4Kβ is a GTP sensor in cells. PI5P4Kβ detects intracellular GTP concentration and controls cell functions via second messenger PI(5)P. Mammalian PI5P4Kβ utilizes GTP as a preferred substrate rather than ATP for its catalytic reaction. Our evolutionary analysis has suggested that PI5P4Kβ evolved from PI4P5K, which is an ATP-dependent kinase. However, it is unclear how and when PI5P4Kβ acquired the GTP-dependent activity in the evolutionary process. To obtain an insight into the evolution of the GTP-dependent activity of PI5P4Kβ, we initiated a comparative structural study of PI5P4K from five evolutionarily important species (human, coelacanth, shark, lancelet and C.elegans). In the crystal structure analysis of PI5P4K, some differences in a loop region, residues 130-137, and conformation of Phe139 were found among the five species (residue numbers for human PI5P4Kβ are used). We found a correlation between the structural changes and GTP-dependent activity of PI5P4K.