6TSZ

The ULK4 Pseudokinase Domain Bound To ATPgammaS

Summary for 6TSZ

• Entry DOI: 10.2210/pdb6tsz/pdb
• Descriptor: Serine/threonine-protein kinase ULK4, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER (3 entities in total)
• Functional Keywords: kinase pseudokinase atp binding hypertension, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 35027.63

Authors

Preuss, F.,Chatterjee, D.,Mathea, S.,Arrowsmith, C.H.,Bountra, C.,Edwards, A.M.,Knapp, S. (deposition date: 2019-12-22, release date: 2020-01-01, Last modification date: 2024-01-24)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)