6TSZ

The ULK4 Pseudokinase Domain Bound To ATPgammaS

6TSZ の概要

• エントリーDOI: 10.2210/pdb6tsz/pdb
• 分子名称: Serine/threonine-protein kinase ULK4, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER (3 entities in total)
• 機能のキーワード: kinase pseudokinase atp binding hypertension, signaling protein
• 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: 35027.63

構造登録者

Preuss, F.,Chatterjee, D.,Mathea, S.,Arrowsmith, C.H.,Bountra, C.,Edwards, A.M.,Knapp, S. (登録日: 2019-12-22, 公開日: 2020-01-01, 最終更新日: 2024-01-24)

主引用文献

Preuss, F.,Chatterjee, D.,Mathea, S.,Shrestha, S.,St-Germain, J.,Saha, M.,Kannan, N.,Raught, B.,Rottapel, R.,Knapp, S.
Nucleotide Binding, Evolutionary Insights, and Interaction Partners of the Pseudokinase Unc-51-like Kinase 4.
Structure, 28:1184-, 2020

PubMed Abstract: Unc-51-like kinase 4 (ULK4) is a pseudokinase that has been linked to the development of several diseases. Even though sequence motifs required for ATP binding in kinases are lacking, ULK4 still tightly binds ATP and the presence of the co-factor is required for structural stability of ULK4. Here, we present a high-resolution structure of a ULK4-ATPγS complex revealing a highly unusual ATP binding mode in which the lack of the canonical VAIK motif lysine is compensated by K39, located N-terminal to αC. Evolutionary analysis suggests that degradation of active site motifs in metazoan ULK4 has co-occurred with an ULK4-specific activation loop, which stabilizes the C helix. In addition, cellular interaction studies using BioID and biochemical validation data revealed high confidence interactors of the pseudokinase and armadillo repeat domains. Many of the identified ULK4 interaction partners were centrosomal and tubulin-associated proteins and several active kinases suggesting interesting regulatory roles for ULK4.

PubMed: 32814032
DOI: 10.1016/j.str.2020.07.016

実験手法

X-RAY DIFFRACTION (1.9 Å)