2ld7

From Proteopedia

(Difference between revisions)

Revision as of 03:53, 25 December 2014

Solution structure of the mSin3A PAH3-SAP30 SID complex

Structural highlights

2ld7 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.
Gene:	Sap30 (Mus musculus), Sin3a, Kiaa4126 (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[SAP30_MOUSE] Involved in the functional recruitment of the Sin3-histone deacetylase complex (HDAC) to a specific subset of N-CoR corepressor complexes. Capable of transcription repression by N-CoR. Active in deacetylating core histone octamers (when in a complex) but inactive in deacetylating nucleosomal histones.^[1] [UniProtKB:O75446] [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]

Publication Abstract from PubMed

The approximately 2-megadalton evolutionarily conserved histone deacetylase-associated Rpd3L/Sin3L complex plays critical roles in altering the histone code and repressing transcription of a broad range of genes involved in many aspects of cellular physiology. Targeting of this complex to specific regions of the genome is presumed to rely on interactions involving one or more of at least 10 distinct subunits in the complex. Here we describe the solution structure of the complex formed by the interacting domains of two constitutively associated subunits, mSin3A and SAP30. The mSin3A paired amphipathic helix 3 (PAH3) domain in the complex adopts the left-handed four-helix bundle structure characteristic of PAH domains. The SAP30 Sin3 interaction domain (SID) binds to PAH3 via a tripartite structural motif, including a C-terminal helix that targets the canonical PAH hydrophobic cleft while two other helices and an N-terminal extension target a discrete surface formed largely by the PAH3 alpha2, alpha3, and alpha3' helices. The protein-protein interface is extensive ( approximately 1400 A(2)), accounting for the high affinity of the interaction and the constitutive association of the SAP30 subunit with the Rpd3L/Sin3L complex. We further show using NMR that the mSin3A PAH3-SAP30 SID complex can bind to nucleic acids, hinting at a role for a nucleolar localization sequence in the SID alphaA helix in targeting the Rpd3L/Sin3L complex for silencing ribosomal RNA genes.

Structure of the 30-kDa Sin3-associated protein (SAP30) in complex with the mammalian Sin3A corepressor and its role in nucleic acid binding.,Xie T, He Y, Korkeamaki H, Zhang Y, Imhoff R, Lohi O, Radhakrishnan I J Biol Chem. 2011 Aug 5;286(31):27814-24. Epub 2011 Jun 15. PMID:21676866^[5]

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

References

↑ Laherty CD, Billin AN, Lavinsky RM, Yochum GS, Bush AC, Sun JM, Mullen TM, Davie JR, Rose DW, Glass CK, Rosenfeld MG, Ayer DE, Eisenman RN. SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors. Mol Cell. 1998 Jul;2(1):33-42. PMID:9702189
↑ 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
↑ Xie T, He Y, Korkeamaki H, Zhang Y, Imhoff R, Lohi O, Radhakrishnan I. Structure of the 30-kDa Sin3-associated protein (SAP30) in complex with the mammalian Sin3A corepressor and its role in nucleic acid binding. J Biol Chem. 2011 Aug 5;286(31):27814-24. Epub 2011 Jun 15. PMID:21676866 doi:10.1074/jbc.M111.252494

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/2ld7"

@@ Line 6: / Line 6: @@
 <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=2ld7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ld7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ld7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ld7 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/SAP30_MOUSE SAP30_MOUSE]] Involved in the functional recruitment of the Sin3-histone deacetylase complex (HDAC) to a specific subset of N-CoR corepressor complexes. Capable of transcription repression by N-CoR. Active in deacetylating core histone octamers (when in a complex) but inactive in deacetylating nucleosomal histones.<ref>PMID:9702189</ref> [UniProtKB:O75446] [[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

2ld7

From Proteopedia

Revision as of 03:53, 25 December 2014

Solution structure of the mSin3A PAH3-SAP30 SID complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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