3hqm

From Proteopedia

(Difference between revisions)

Revision as of 07:01, 25 December 2014

Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases: SPOPMATHx-CiSBC2

Structural highlights

3hqm is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	SPOP (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[SPOP_HUMAN] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.^[1] ^[2] ^[3] [CI_DROME] Has a dual function as a transcriptional activator and a repressor of the hedgehog (Hh) pathway. The full-length ci form (ciFL), acts as an activator (ciA) while ciR, its C-terminally truncated form, acts as a repressor. Involved in segment polarity. Required for the normal development of the posterior half of each embryonic segment. Engrailed protein directly represses ci expression in posterior compartment cells.

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 PubMed

In the largest E3 ligase subfamily, Cul3 binds a BTB domain, and an associated protein-interaction domain such as MATH recruits substrates for ubiquitination. Here, we present biochemical and structural analyses of the MATH-BTB protein, SPOP. We define a SPOP-binding consensus (SBC) and determine structures revealing recognition of SBCs from the phosphatase Puc, the transcriptional regulator Ci, and the chromatin component MacroH2A. We identify a dimeric SPOP-Cul3 assembly involving a conserved helical structure C-terminal of BTB domains, which we call "3-box" due to its facilitating Cul3 binding and its resemblance to F-/SOCS-boxes in other cullin-based E3s. Structural flexibility between the substrate-binding MATH and Cul3-binding BTB/3-box domains potentially allows a SPOP dimer to engage multiple SBCs found within a single substrate, such as Puc. These studies provide a molecular understanding of how MATH-BTB proteins recruit substrates to Cul3 and how their dimerization and conformational variability may facilitate avid interactions with diverse substrates.

Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases.,Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN, Hoggard T, Harper JW, White KP, Schulman BA Mol Cell. 2009 Oct 9;36(1):39-50. PMID:19818708^[4]

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

References

↑ Furukawa M, He YJ, Borchers C, Xiong Y. Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat Cell Biol. 2003 Nov;5(11):1001-7. Epub 2003 Oct 5. PMID:14528312 doi:10.1038/ncb1056
↑ Hernandez-Munoz I, Lund AH, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, Nusinow DA, Panning B, Marahrens Y, van Lohuizen M. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7635-40. Epub 2005 May 16. PMID:15897469 doi:0408918102
↑ Kwon JE, La M, Oh KH, Oh YM, Kim GR, Seol JH, Baek SH, Chiba T, Tanaka K, Bang OS, Joe CO, Chung CH. BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase. J Biol Chem. 2006 May 5;281(18):12664-72. Epub 2006 Mar 8. PMID:16524876 doi:10.1074/jbc.M600204200
↑ Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN, Hoggard T, Harper JW, White KP, Schulman BA. Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Mol Cell. 2009 Oct 9;36(1):39-50. PMID:19818708 doi:10.1016/j.molcel.2009.09.022

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3hqm"

@@ Line 7: / Line 7: @@
 <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=3hqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hqm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hqm RCSB], [http://www.ebi.ac.uk/pdbsum/3hqm PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/SPOP_HUMAN SPOP_HUMAN]] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.<ref>PMID:14528312</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref>  [[http://www.uniprot.org/uniprot/CI_DROME CI_DROME]] Has a dual function as a transcriptional activator and a repressor of the hedgehog (Hh) pathway. The full-length ci form (ciFL), acts as an activator (ciA) while ciR, its C-terminally truncated form, acts as a repressor. Involved in segment polarity. Required for the normal development of the posterior half of each embryonic segment. Engrailed protein directly represses ci expression in posterior compartment cells.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3hqm

From Proteopedia

Revision as of 07:01, 25 December 2014

Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases: SPOPMATHx-CiSBC2

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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