1s5r

From Proteopedia

(Difference between revisions)

Revision as of 00:20, 25 December 2014

Solution Structure of HBP1 SID-mSin3A PAH2 Complex

Structural highlights

1s5r is a 2 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1s5q
Gene:	Sin3A (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[HBP1_MOUSE] Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the H1F0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4 (By similarity).^[1] [SIN3A_MOUSE] Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation.^[2] ^[3] ^[4]

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

Recruitment of the histone deacetylase (HDAC)-associated Sin3 corepressor is an obligatory step in many eukaryotic gene silencing pathways. Here we show that HBP1, a cell cycle inhibitor and regulator of differentiation, represses transcription in a HDAC/Sin3-dependent manner by targeting the mammalian Sin3A (mSin3A) PAH2 domain. HBP1 is unrelated to the Mad1 repressor for which high-resolution structures in complex with PAH2 have been described. We show that like Mad1, the HBP1 transrepression domain binds through a helical structure to the hydrophobic cleft of mSin3A PAH2. Notably, the HBP1 helix binds PAH2 in a reversed orientation relative to Mad1 and, equally unexpectedly, this is correlated with a chain reversal of the minimal Sin3 interaction motifs. These results not only provide insights into how multiple, unrelated transcription factors recruit the same coregulator, but also have implications for how sequence similarity searches are conducted.

HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations.,Swanson KA, Knoepfler PS, Huang K, Kang RS, Cowley SM, Laherty CD, Eisenman RN, Radhakrishnan I Nat Struct Mol Biol. 2004 Aug;11(8):738-46. Epub 2004 Jul 4. PMID:15235594^[5]

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

References

↑ Lavender P, Vandel L, Bannister AJ, Kouzarides T. The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A. Oncogene. 1997 Jun 5;14(22):2721-8. PMID:9178770 doi:http://dx.doi.org/10.1038/sj.onc.1201243
↑ Rao G, Alland L, Guida P, Schreiber-Agus N, Chen K, Chin L, Rochelle JM, Seldin MF, Skoultchi AI, DePinho RA. Mouse Sin3A interacts with and can functionally substitute for the amino-terminal repression of the Myc antagonist Mxi1. Oncogene. 1996 Mar 7;12(5):1165-72. PMID:8649810
↑ Ayer DE, Lawrence QA, Eisenman RN. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell. 1995 Mar 10;80(5):767-76. PMID:7889570
↑ Grimes JA, Nielsen SJ, Battaglioli E, Miska EA, Speh JC, Berry DL, Atouf F, Holdener BC, Mandel G, Kouzarides T. The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex. J Biol Chem. 2000 Mar 31;275(13):9461-7. PMID:10734093
↑ Swanson KA, Knoepfler PS, Huang K, Kang RS, Cowley SM, Laherty CD, Eisenman RN, Radhakrishnan I. HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations. Nat Struct Mol Biol. 2004 Aug;11(8):738-46. Epub 2004 Jul 4. PMID:15235594 doi:10.1038/nsmb798

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/1s5r"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1s5r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1S5R FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1s5q|1s5q]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1s5q|1s5q]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sin3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sin3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s5r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1s5r RCSB], [http://www.ebi.ac.uk/pdbsum/1s5r PDBsum]</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=1s5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s5r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1s5r RCSB], [http://www.ebi.ac.uk/pdbsum/1s5r PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/HBP1_MOUSE HBP1_MOUSE]] Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the H1F0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4 (By similarity).<ref>PMID:9178770</ref>  [[http://www.uniprot.org/uniprot/SIN3A_MOUSE SIN3A_MOUSE]] Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation.<ref>PMID:8649810</ref> <ref>PMID:7889570</ref> <ref>PMID:10734093</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 30: / Line 32: @@
 </StructureSection>
 [[Category: Mus musculus]]
-[[Category: Cowley, S M.]]
+[[Category: Cowley, S M]]
-[[Category: Eisenman, R N.]]
+[[Category: Eisenman, R N]]
-[[Category: Huang, K.]]
+[[Category: Huang, K]]
-[[Category: Kang, R S.]]
+[[Category: Kang, R S]]
-[[Category: Knoepfler, P S.]]
+[[Category: Knoepfler, P S]]
-[[Category: Laherty, C D.]]
+[[Category: Laherty, C D]]
-[[Category: Radhakrishnan, I.]]
+[[Category: Radhakrishnan, I]]
-[[Category: Swanson, K A.]]
+[[Category: Swanson, K A]]
 [[Category: Amphipathic helix motif]]
 [[Category: Four-helix bundle]]

1s5r

From Proteopedia

Revision as of 00:20, 25 December 2014

Solution Structure of HBP1 SID-mSin3A PAH2 Complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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