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Crystal structure of the Cbk1(T743E)-Mob2 kinase-coactivator complex in crystal form BCrystal structure of the Cbk1(T743E)-Mob2 kinase-coactivator complex in crystal form B
Structural highlights
Function[CBK1_YEAST] Protein kinase that seems to play a role in the regulation of cell morphogenesis and proliferation. [MOB2_YEAST] Functions as an activator subunit for the CBK1 protein kinase. Part of the regulation of ACE2 activity and cellular morphogenesis (RAM) signaling network. Required for coordinating polarized cell growth during interphase with the onset of mitosis. Required for mother/daughter cell separation after cytokinesis. Also has a role in the prevention of nuclear export of ACE2 from the daughter cell nucleus after mitotic exit. It coordinates ACE2-dependent transcription with mitotic exit network activation.[1] [2] Publication Abstract from PubMedEukaryotic cells commonly use protein kinases in signaling systems that relay information and control a wide range of processes. These enzymes have a fundamentally similar structure, but achieve functional diversity through variable regions that determine how the catalytic core is activated and recruited to phosphorylation targets. "Hippo" pathways are ancient protein kinase signaling systems that control cell proliferation and morphogenesis; the NDR/LATS family protein kinases, which associate with "Mob" coactivator proteins, are central but incompletely understood components of these pathways. Here we describe the crystal structure of budding yeast Cbk1-Mob2, to our knowledge the first of an NDR/LATS kinase-Mob complex. It shows a novel coactivator-organized activation region that may be unique to NDR/LATS kinases, in which a key regulatory motif apparently shifts from an inactive binding mode to an active one upon phosphorylation. We also provide a structural basis for a substrate docking mechanism previously unknown in AGC family kinases, and show that docking interaction provides robustness to Cbk1's regulation of its two known in vivo substrates. Co-evolution of docking motifs and phosphorylation consensus sites strongly indicates that a protein is an in vivo regulatory target of this hippo pathway, and predicts a new group of high-confidence Cbk1 substrates that function at sites of cytokinesis and cell growth. Moreover, docking peptides arise in unstructured regions of proteins that are probably already kinase substrates, suggesting a broad sequential model for adaptive acquisition of kinase docking in rapidly evolving intrinsically disordered polypeptides. The Structure of an NDR/LATS Kinase-Mob Complex Reveals a Novel Kinase-Coactivator System and Substrate Docking Mechanism.,Gogl G, Schneider KD, Yeh BJ, Alam N, Nguyen Ba AN, Moses AM, Hetenyi C, Remenyi A, Weiss EL PLoS Biol. 2015 May 12;13(5):e1002146. doi: 10.1371/journal.pbio.1002146., eCollection 2015 May. PMID:25966461[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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