3A60

Crystal structure of unphosphorylated p70S6K1 (Form I)

3A60 の概要

• エントリーDOI: 10.2210/pdb3a60/pdb
• 関連するPDBエントリー: 3A61 3A62
• 分子名称: Ribosomal protein S6 kinase beta-1, STAUROSPORINE (3 entities in total)
• 機能のキーワード: kinase, kinase domain, inactive, active, ribosomal s6 kinase, activation, alternative initiation, atp-binding, cell junction, cytoplasm, nucleotide-binding, phosphoprotein, polymorphism, serine/threonine-protein kinase, synapse, synaptosome, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell junction, synapse, synaptosome . Isoform Alpha I: Nucleus. Isoform Alpha II: Cytoplasm: P23443
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74806.34

構造登録者

Sunami, T.,Byrne, N.,Diehl, R.E.,Funabashi, K.,Hall, D.L.,Ikuta, M.,Patel, S.B.,Shipman, J.M.,Smith, R.F.,Takahashi, I.,Zugay-Murphy, J.,Iwasawa, Y.,Lumb, K.J.,Munshi, S.K.,Sharma, S. (登録日: 2009-08-17, 公開日: 2009-10-27, 最終更新日: 2023-11-01)

主引用文献

Sunami, T.,Byrne, N.,Diehl, R.E.,Funabashi, K.,Hall, D.L.,Ikuta, M.,Patel, S.B.,Shipman, J.M.,Smith, R.F.,Takahashi, I.,Zugay-Murphy, J.,Iwasawa, Y.,Lumb, K.J.,Munshi, S.K.,Sharma, S.
Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation.
J.Biol.Chem., 285:4587-4594, 2010

PubMed Abstract: p70 ribosomal S6 kinase (p70S6K) is a downstream effector of the mTOR signaling pathway involved in cell proliferation, cell growth, cell-cycle progression, and glucose homeostasis. Multiple phosphorylation events within the catalytic, autoinhibitory, and hydrophobic motif domains contribute to the regulation of p70S6K. We report the crystal structures of the kinase domain of p70S6K1 bound to staurosporine in both the unphosphorylated state and in the 3'-phosphoinositide-dependent kinase-1-phosphorylated state in which Thr-252 of the activation loop is phosphorylated. Unphosphorylated p70S6K1 exists in two crystal forms, one in which the p70S6K1 kinase domain exists as a monomer and the other as a domain-swapped dimer. The crystal structure of the partially activated kinase domain that is phosphorylated within the activation loop reveals conformational ordering of the activation loop that is consistent with a role in activation. The structures offer insights into the structural basis of the 3'-phosphoinositide-dependent kinase-1-induced activation of p70S6K and provide a platform for the rational structure-guided design of specific p70S6K inhibitors.

PubMed: 19864428
DOI: 10.1074/jbc.M109.040667

実験手法

X-RAY DIFFRACTION (2.8 Å)