4FVP

Crystal structure of the Jak2 pseudokinase domain (apo form)

4FVP の概要

• エントリーDOI: 10.2210/pdb4fvp/pdb
• 関連するPDBエントリー: 4FVQ 4FVR
• 分子名称: Tyrosine-protein kinase JAK2, GLYCEROL (3 entities in total)
• 機能のキーワード: janus protein kinase, pseudokinase, atp binding, phosphorylation, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endomembrane system; Peripheral membrane protein (By similarity): O60674
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33305.15

構造登録者

Bandaranayake, R.M.,Hubbard, S.R. (登録日: 2012-06-29, 公開日: 2012-07-25, 最終更新日: 2023-09-13)

主引用文献

Bandaranayake, R.M.,Ungureanu, D.,Shan, Y.,Shaw, D.E.,Silvennoinen, O.,Hubbard, S.R.
Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F.
Nat.Struct.Mol.Biol., 19:754-759, 2012

PubMed Abstract: The protein tyrosine kinase JAK2 mediates signaling through numerous cytokine receptors. JAK2 possesses a pseudokinase domain (JH2) and a tyrosine kinase domain (JH1). Through unknown mechanisms, JH2 regulates the catalytic activity of JH1, and hyperactivating mutations in the JH2 region of human JAK2 cause myeloproliferative neoplasms (MPNs). We showed previously that JAK2 JH2 is, in fact, catalytically active. Here we present crystal structures of human JAK2 JH2, including both wild type and the most prevalent MPN mutant, V617F. The structures reveal that JH2 adopts the fold of a prototypical protein kinase but binds Mg-ATP noncanonically. The structural and biochemical data indicate that the V617F mutation rigidifies α-helix C in the N lobe of JH2, facilitating trans-phosphorylation of JH1. The crystal structures of JH2 afford new opportunities for the design of novel JAK2 therapeutics targeting MPNs.

PubMed: 22820988
DOI: 10.1038/nsmb.2348

実験手法

X-RAY DIFFRACTION (2.01 Å)