Mob-family kinase co-activators bind cognate Ndr/Lats kinases through conserved and modular interface

Parker, B.; Gogl, G.; Balint, M.; Hetenyi, C.; Remenyi, A.; Weiss, E.

doi:10.1101/242115

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bioRxiv · 10.1101/242115

Mob-family kinase co-activators bind cognate Ndr/Lats kinases through conserved and modular interface

Parker, B.·Gogl, G.·Balint, M.·Hetenyi, C.·Remenyi, A.·Weiss, E.

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Abstract

Ndr/Lats kinases bind to Mob coactivator proteins and their complexes play important roles in \"Hippo\" signaling pathways controlling cell proliferation and morphogenesis. All Ndr/Lats kinases have a 70-80 amino acid long unique N-terminal region (NTR) which binds to Mob factors. In order to gain insight into the structural basis of kinase-coactivator binding specificity, we have determined the crystal structure of Cbk1(NTR)-Mob2 and Dbf2(NTR)-Mob1 complexes from yeast (S. cerevisiae). We show that the Ndr/Lats(NTR)-Mob interface is a common structural platform through which kinase-cofactor binding is mediated, albeit amino acid variations in key positions contribute to subgroup and organism-specific differences. We further show that conserved residues at the NTR-Mob interface may participate in novel activation mechanisms likely ubiquitous in Ndr/Lats kinases. Ndr/Lats kinase activation may resemble to that of other AGC kinases but with an extra structural requirement for NTR mediated Mob binding for proper allosteric activation.

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Parker, B., Gogl, G., Balint, M., Hetenyi, C., Remenyi, A., Weiss, E.. 2018-04-25. Mob-family kinase co-activators bind cognate Ndr/Lats kinases through conserved and modular interface. https://doi.org/10.1101/242115

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