5NCM

Crystal structure Cbk1(NTR)-Mob2 complex

Summary for 5NCM

• Entry DOI: 10.2210/pdb5ncm/pdb
• Descriptor: CBK1 kinase activator protein MOB2, Serine/threonine-protein kinase CBK1, ZINC ION (3 entities in total)
• Functional Keywords: signaling protein, kinase
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 40747.37

Authors

Gogl, G.,Remenyi, A.,Parker, B.,Weiss, E. (deposition date: 2017-03-06, release date: 2018-05-16, Last modification date: 2024-01-17)

Primary citation

Parker, B.W.,Gogl, G.,Balint, M.,Hetenyi, C.,Remenyi, A.,Weiss, E.L.
Ndr/Lats Kinases Bind Specific Mob-Family Coactivators through a Conserved and Modular Interface.
Biochemistry, 2020

PubMed Abstract: Ndr/Lats kinases bind Mob coactivator proteins to form complexes that are essential and evolutionarily conserved components of "Hippo" signaling pathways, which control cell proliferation and morphogenesis in eukaryotes. All Ndr/Lats kinases have a characteristic N-terminal regulatory (NTR) region that binds a specific Mob cofactor: Lats kinases associate with Mob1 proteins, and Ndr kinases associate with Mob2 proteins. To better understand the significance of the association of Mob protein with Ndr/Lats kinases and selective binding of Ndr and Lats to distinct Mob cofactors, we determined crystal structures of Cbk1-Mob2 and Dbf2-Mob1 and experimentally assessed determinants of Mob cofactor binding and specificity. This allowed a significant improvement in the previously determined structure of Cbk1 kinase bound to Mob2, presently the only crystallographic model of a full length Ndr/Lats kinase complexed with a Mob cofactor. Our analysis indicates that the Ndr/Lats-Mob interface provides a distinctive kinase regulation mechanism, in which the Mob cofactor organizes the Ndr/Lats NTR to interact with the AGC kinase C-terminal hydrophobic motif (HM), which is involved in allosteric regulation. The Mob-organized NTR appears to mediate association of the HM with an allosteric site on the N-terminal kinase lobe. We also found that Cbk1 and Dbf2 associated specifically with Mob2 and Mob1, respectively. Alteration of residues in the Cbk1 NTR allows association of the noncognate Mob cofactor, indicating that cofactor specificity is restricted by discrete sites rather than being broadly distributed. Overall, our analysis provides a new picture of the functional role of Mob association and indicates that the Ndr/Lats-Mob interface is largely a common structural platform that mediates kinase-cofactor binding.

PubMed: 32250593
DOI: 10.1021/acs.biochem.9b01096

Experimental method

X-RAY DIFFRACTION (2.8 Å)