6UNR

Kinase domain of ALK2-K492A/K493A with AMPPNP

6UNR の概要

• エントリーDOI: 10.2210/pdb6unr/pdb
• 関連するPDBエントリー: 6UNQ
• 分子名称: Activin receptor type-1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38759.97

構造登録者

Agnew, C.,Jura, N. (登録日: 2019-10-13, 公開日: 2021-07-07, 最終更新日: 2023-10-11)

主引用文献

Agnew, C.,Ayaz, P.,Kashima, R.,Loving, H.S.,Ghatpande, P.,Kung, J.E.,Underbakke, E.S.,Shan, Y.,Shaw, D.E.,Hata, A.,Jura, N.
Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization.
Nat Commun, 12:4950-4950, 2021

PubMed Abstract: Upon ligand binding, bone morphogenetic protein (BMP) receptors form active tetrameric complexes, comprised of two type I and two type II receptors, which then transmit signals to SMAD proteins. The link between receptor tetramerization and the mechanism of kinase activation, however, has not been elucidated. Here, using hydrogen deuterium exchange mass spectrometry (HDX-MS), small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, combined with analysis of SMAD signaling, we show that the kinase domain of the type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes. Formation of this dimer is essential for ligand-induced receptor signaling and is targeted by mutations in BMPR2 in patients with pulmonary arterial hypertension (PAH). We further show that the type I/type II kinase domain heterodimer serves as the scaffold for assembly of the active tetrameric receptor complexes to enable phosphorylation of the GS domain and activation of SMADs.

PubMed: 34400635
DOI: 10.1038/s41467-021-25248-5

実験手法

X-RAY DIFFRACTION (2.2 Å)