1pi1
From Proteopedia
Crystal structure of a human Mob1 protein; toward understanding Mob-regulated cell cycle pathways.
Structural highlights
FunctionMOB1A_HUMAN Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Mob protein family comprises a group of highly conserved eukaryotic proteins whose founding member functions in the mitotic exit network. At the molecular level, Mob proteins act as kinase-activating subunits. We cloned a human Mob1 family member, Mob1A, and determined its three-dimensional structure by X-ray crystallography. The core of Mob1A consists of a four-helix bundle that is stabilized by a bound zinc atom. The N-terminal helix of the bundle is solvent exposed and together with adjacent secondary structure elements forms an evolutionarily conserved surface with a strong negative electrostatic potential. Several conditional mutant alleles of S. cerevisiae MOB1 target this surface and decrease its net negative charge. Interestingly, the kinases with which yeast Mob proteins interact have two conserved basic regions within their N-terminal lobe. Thus, Mob proteins may regulate their target kinases through electrostatic interactions mediated by conserved charged surfaces. Crystal structure of a human Mob1 protein: toward understanding Mob-regulated cell cycle pathways.,Stavridi ES, Harris KG, Huyen Y, Bothos J, Verwoerd PM, Stayrook SE, Pavletich NP, Jeffrey PD, Luca FC Structure. 2003 Sep;11(9):1163-70. PMID:12962634[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Bothos J | Harris KG | Huyen Y | Jeffrey PD | Luca FC | Pavletich NP | Stavridi ES | Stayrook SE | Voewerd PM
