5b6b

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(Difference between revisions)

Revision as of 10:06, 26 February 2020

Complex of LATS1 and phosphomimetic MOB1b

Structural highlights

5b6b is a 16 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5b5v, 5b5w
Gene:	Mob1b, Mobkl1a (LK3 transgenic mice), Lats1, Warts (LK3 transgenic mice)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MOB1B_MOUSE] 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 STK38L (By similarity). [LATS1_MOUSE] Negative regulator of YAP1 in the Hippo signaling pathway that 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 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function (By similarity).^[1]

Publication Abstract from PubMed

MOB1 protein is a key regulator of large tumor suppressor 1/2 (LATS1/2) kinases in the Hippo pathway. MOB1 is present in an autoinhibited form and is activated by MST1/2-mediated phosphorylation, although the precise mechanisms responsible for autoinhibition and activation are unknown due to lack of an autoinhibited MOB1 structure. Here, we report on the crystal structure of full-length MOB1B in the autoinhibited form and a complex between the MOB1B core domain and the N-terminal regulation (NTR) domain of LATS1. The structure of full-length MOB1B shows that the N-terminal extension forms a short beta-strand, the SN strand, followed by a long conformationally flexible positively-charged linker and alpha-helix, the Switch helix, which blocks the LATS1 binding surface of MOB1B. The Switch helix is stabilized by beta-sheet formation of the SN strand with the S2 strand of the MOB1 core domain. Phosphorylation of Thr12 and Thr35 residues structurally accelerates dissociation of the Switch helix from the LATS1-binding surface by the "pull-the-string" mechanism, thereby enabling LATS1 binding.

Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway.,Kim SY, Tachioka Y, Mori T, Hakoshima T Sci Rep. 2016 Jun 23;6:28488. doi: 10.1038/srep28488. PMID:27335147^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ St John MA, Tao W, Fei X, Fukumoto R, Carcangiu ML, Brownstein DG, Parlow AF, McGrath J, Xu T. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat Genet. 1999 Feb;21(2):182-6. PMID:9988269 doi:http://dx.doi.org/10.1038/5965
↑ Kim SY, Tachioka Y, Mori T, Hakoshima T. Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway. Sci Rep. 2016 Jun 23;6:28488. doi: 10.1038/srep28488. PMID:27335147 doi:http://dx.doi.org/10.1038/srep28488

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5b6b"

@@ Line 1: / Line 1: @@
 ==Complex of LATS1 and phosphomimetic MOB1b==
-<StructureSection load='5b6b' size='340' side='right' caption='[[5b6b]], [[Resolution|resolution]] 3.54&Aring;' scene=''>
+<StructureSection load='5b6b' size='340' side='right'caption='[[5b6b]], [[Resolution|resolution]] 3.54&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5b6b]] is a 16 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B6B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B6B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5b6b]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B6B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B6B FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5b5v|5b5v]], [[5b5w|5b5w]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mob1b, Mobkl1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Lats1, Warts ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5b6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b6b OCA], [http://pdbe.org/5b6b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b6b RCSB], [http://www.ebi.ac.uk/pdbsum/5b6b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b6b ProSAT]</span></td></tr>
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5b6b" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Hakoshima, T]]

5b6b

From Proteopedia

Revision as of 10:06, 26 February 2020

Complex of LATS1 and phosphomimetic MOB1b

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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