PDBsum entry 4lqq

Transferase/transferase activator

PDB id: 4lqq

Contents

Protein chains

388 a.a.

146 a.a.

329 a.a.

137 a.a.

Ligands

ANP

PDB id:

4lqq

Name:

Transferase/transferase activator

Title:

Crystal structure of the cbk1(t743e)-mob2 kinase-coactivator complex in crystal form b

Structure:

Serine/threonine-protein kinase cbk1. Chain: a, d. Fragment: unp residues 251-756. Synonym: cell wall biosynthesis kinase. Engineered: yes. Mutation: yes. Cbk1 kinase activator protein mob2. Chain: b, e. Fragment: unp residues 46-287.

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 559292. Strain: atcc 204508 / s288c. Gene: cbk1, n1727, ynl161w. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: mob2, yfl034c-b, yfl035c, yfl035c-a. Expression_system_taxid: 562

Resolution:

3.60Å R-factor: 0.262 R-free: 0.319

Authors:

G.Gogl,A.Remenyi

Key ref:

G.Gógl et al. (2015). The Structure of an NDR/LATS Kinase-Mob Complex Reveals a Novel Kinase-Coactivator System and Substrate Docking Mechanism. Plos Biol, 13, e1002146. PubMed id: 25966461 DOI: 10.1371/journal.pbio.1002146

Date:

19-Jul-13 Release date: 30-Jul-14

Protein chain

P53894  (CBK1_YEAST) -  Serine/threonine-protein kinase CBK1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 756 a.a.

Struc: 388 a.a.*

Protein chain

P43563  (MOB2_YEAST) -  CBK1 kinase activator protein MOB2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 287 a.a.

Struc: 146 a.a.

Protein chain

P53894  (CBK1_YEAST) -  Serine/threonine-protein kinase CBK1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 756 a.a.

Struc: 329 a.a.*

Protein chain

P43563  (MOB2_YEAST) -  CBK1 kinase activator protein MOB2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 287 a.a.

Struc: 137 a.a.

* PDB and UniProt seqs differ at 13 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, D: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1371/journal.pbio.1002146

Plos Biol 13:e1002146 (2015)

PubMed id: 25966461

The Structure of an NDR/LATS Kinase-Mob Complex Reveals a Novel Kinase-Coactivator System and Substrate Docking Mechanism.

G.Gógl, K.D.Schneider, B.J.Yeh, N.Alam, A.N.Nguyen Ba, A.M.Moses, C.Hetényi, A.Reményi, E.L.Weiss.

ABSTRACT

Eukaryotic 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.