2QLU

Crystal structure of Activin receptor type II kinase domain from human

2QLU の概要

• エントリーDOI: 10.2210/pdb2qlu/pdb
• 分子名称: Activin receptor type IIB, SULFATE ION, ADENINE, ... (4 entities in total)
• 機能のキーワード: tgf-beta, actriib, serine/threonine kinase receptor, alternative splicing, atp-binding, disease mutation, glycoprotein, magnesium, manganese, membrane, metal-binding, nucleotide-binding, serine/threonine-protein kinase, transferase, transmembrane
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: Q13705
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36123.28

構造登録者

Han, S. (登録日: 2007-07-13, 公開日: 2007-11-20, 最終更新日: 2024-02-21)

主引用文献

Han, S.,Loulakis, P.,Griffor, M.,Xie, Z.
Crystal structure of activin receptor type IIB kinase domain from human at 2.0 Angstrom resolution
Protein Sci., 16:2272-2277, 2007

PubMed Abstract: Activin receptor type IIB (ActRIIB), a type II TGF-beta serine/threonine kinase receptor, is integral to the activin and myostatin signaling pathway. Ligands such as activin and myostatin bind to activin type II receptors (ActRIIA, ActRIIB), and the GS domains of type I receptors are phosphorylated by type II receptors. Myostatin, a negative regulator of skeletal muscle growth, is regarded as a potential therapeutic target and binds to ActRIIB effectively, and to a lesser extent, to ActRIIA. The high-resolution structure of human ActRIIB kinase domain in complex with adenine establishes the conserved bilobal architecture consistent with all other catalytic kinase domains. The crystal structure reveals that the adenine has a considerably different orientation from that of the adenine moiety of ATP observed in other kinase structures due to the lack of an interaction by ribose-phosphate moiety and the presence of tautomers with two different protonation states at the N9 nitrogen. Although the Lys217-Glu230 salt bridge is absent, the unphosphorylated activation loop of ActRIIB adopts a conformation similar to that of the fully active form. Unlike the type I TGF-beta receptor, where a partially conserved Ser280 is a gatekeeper residue, the AcRIIB structure possesses Thr265 with a back pocket supported by Phe247. Taken together, these structural features provide a molecular basis for understanding the coupled activity and recognition specificity for human ActRIIB kinase domain and for the rational design of selective inhibitors.

PubMed: 17893364
DOI: 10.1110/ps.073068407

実験手法

X-RAY DIFFRACTION (2 Å)