7EM5

Crystal structure of the PI5P4Kbeta F205L-XTP complex

Summary for 7EM5

• Entry DOI: 10.2210/pdb7em5/pdb
• Descriptor: Phosphatidylinositol 5-phosphate 4-kinase type-2 beta, [(2~{R},3~{S},4~{R},5~{R})-5-[2,6-bis(oxidanylidene)-3~{H}-purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl phosphono hydrogen phosphate, [[(2~{R},3~{S},4~{R},5~{R})-5-[2,6-bis(oxidanylidene)-3~{H}-purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] phosphono hydrogen phosphate, ... (4 entities in total)
• Functional Keywords: lipid kinase, phosphoinositide signaling, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 91202.31

Authors

Senda, M.,Senda, T. (deposition date: 2021-04-13, release date: 2022-03-30, Last modification date: 2023-11-29)

Primary citation

Takeuchi, K.,Ikeda, Y.,Senda, M.,Harada, A.,Okuwaki, K.,Fukuzawa, K.,Nakagawa, S.,Yu, H.Y.,Nagase, L.,Imai, M.,Sasaki, M.,Lo, Y.H.,Ito, D.,Osaka, N.,Fujii, Y.,Sasaki, A.T.,Senda, T.
The GTP responsiveness of PI5P4K beta evolved from a compromised trade-off between activity and specificity.
Structure, 30:886-899.e4, 2022

PubMed Abstract: Unlike most kinases, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) utilizes GTP as a physiological phosphate donor and regulates cell growth under stress (i.e., GTP-dependent stress resilience). However, the genesis and evolution of its GTP responsiveness remain unknown. Here, we reveal that PI5P4Kβ has acquired GTP preference by generating a short dual-nucleotide-recognizing motif called the guanine efficient association (GEA) motif. Comparison of nucleobase recognition with 660 kinases and 128 G proteins has uncovered that most kinases and PI5P4Kβ use their main-chain atoms for adenine recognition, while the side-chain atoms are required for guanine recognition. Mutational analysis of the GEA motif revealed that the acquisition of GTP reactivity is accompanied by an extended activity toward inosine triphosphate (ITP) and xanthosine triphosphate (XTP). Along with the evolutionary analysis data that point to strong negative selection of the GEA motif, these results suggest that the GTP responsiveness of PI5P4Kβ has evolved from a compromised trade-off between activity and specificity, underpinning the development of the GTP-dependent stress resilience.

PubMed: 35504278
DOI: 10.1016/j.str.2022.04.004

Experimental method

X-RAY DIFFRACTION (2.8 Å)