TY  - JOUR
A1  - Preuß, Franziska Friederike
A1  - Chatterjee, Deep
A1  - Mathea, Sebastian
A1  - Shrestha, Safal
A1  - St-Germain, Jonathan
A1  - Saha, Manipa
A1  - Kannan, Natarajan
A1  - Raught, Brian
A1  - Rottapel, Robert
A1  - Knapp, Stefan
T1  - Nucleotide binding, evolutionary insights, and interaction partners of the pseudokinase Unc-51-like kinase 4
T2  - Structure
N2  - 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.
KW  - Unc-51-like kinase
KW  - ULK4
KW  - pseudokinase
KW  - evolution
KW  - BioID
KW  - ATP binding
KW  - interaction partners
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62553
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-625537
UR  - https://www.sgc-frankfurt.de/pdfs/Others/Preuss_etal_2020_Nucelotide_Binding_aam2.pdf
N1  - Erschienen in: Franziska Preuss et al. (2020): Nucleotide Binding, Evolutionary Insights, and Interaction Partners of the Pseudokinase Unc-51-like Kinase 4. Structure, 28, 1184–1196.e6. https://doi.org/10.1016/j.str.2020.07.016
VL  - 28
IS  - 11
SP  - 1184
EP  - 1196.e6
PB  - Elsevier Science
CY  - London [u.a.]
ER  -