6tsz
From Proteopedia
The ULK4 Pseudokinase Domain Bound To ATPgammaS
Structural highlights
DiseaseULK4_HUMAN Various anomalies in ULK4 gene have been reported for several cases of schizophrenia, schizophrenia plus bipolar disorder and autism. ULK4 gene has been proposed to be a rare susceptibility risk factor for a range of psychiatric diseases including schizophrenia.[1] FunctionULK4_HUMAN May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.[2] Publication Abstract from PubMedUnc-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-ATPgammaS 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 alphaC. 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. Nucleotide Binding, Evolutionary Insights, and Interaction Partners of the Pseudokinase Unc-51-like Kinase 4.,Preuss F, Chatterjee D, Mathea S, Shrestha S, St-Germain J, Saha M, Kannan N, Raught B, Rottapel R, Knapp S Structure. 2020 Aug 13. pii: S0969-2126(20)30280-X. doi:, 10.1016/j.str.2020.07.016. PMID:32814032[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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