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| | <StructureSection load='1jfi' size='340' side='right'caption='[[1jfi]], [[Resolution|resolution]] 2.62Å' scene=''> | | <StructureSection load='1jfi' size='340' side='right'caption='[[1jfi]], [[Resolution|resolution]] 2.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1jfi]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The July 2005 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''TATA-Binding Protein'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2005_7 10.2210/rcsb_pdb/mom_2005_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JFI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1JFI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1jfi]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2005 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''TATA-Binding Protein'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2005_7 10.2210/rcsb_pdb/mom_2005_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JFI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NC2 alpha (DRAP1) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NC2 beta (Dr1) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), tbp ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.62Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1jfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jfi OCA], [http://pdbe.org/1jfi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jfi RCSB], [http://www.ebi.ac.uk/pdbsum/1jfi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jfi ProSAT], [http://www.topsan.org/Proteins/NYSGXRC/1jfi TOPSAN]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jfi OCA], [https://pdbe.org/1jfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jfi RCSB], [https://www.ebi.ac.uk/pdbsum/1jfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jfi ProSAT], [https://www.topsan.org/Proteins/NYSGXRC/1jfi TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/TBP_HUMAN TBP_HUMAN]] Defects in TBP are the cause of spinocerebellar ataxia type 17 (SCA17) [MIM:[http://omim.org/entry/607136 607136]]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA17 is an autosomal dominant cerebellar ataxia (ADCA) characterized by widespread cerebral and cerebellar atrophy, dementia and extrapyramidal signs. The molecular defect in SCA17 is the expansion of a CAG repeat in the coding region of TBP. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:11313753</ref> <ref>PMID:11448935</ref> <ref>PMID:11939898</ref> | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NC2B_HUMAN NC2B_HUMAN]] The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.<ref>PMID:8670811</ref> <ref>PMID:19103755</ref> [[http://www.uniprot.org/uniprot/NC2A_HUMAN NC2A_HUMAN]] The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own.<ref>PMID:8670811</ref> <ref>PMID:8608938</ref> [[http://www.uniprot.org/uniprot/TBP_HUMAN TBP_HUMAN]] General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID. Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.<ref>PMID:15970593</ref> | + | [https://www.uniprot.org/uniprot/NC2A_HUMAN NC2A_HUMAN] The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own.<ref>PMID:8670811</ref> <ref>PMID:8608938</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| | [[Category: TATA-Binding Protein]] | | [[Category: TATA-Binding Protein]] |
| - | [[Category: Burley, S K]] | + | [[Category: Burley SK]] |
| - | [[Category: Chen, H]] | + | [[Category: Chen H]] |
| - | [[Category: Kamada, K]] | + | [[Category: Kamada K]] |
| - | [[Category: Malik, S]] | + | [[Category: Malik S]] |
| - | [[Category: Meisterernst, M]] | + | [[Category: Meisterernst M]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Roeder RG]] |
| - | [[Category: Roeder, R G]] | + | [[Category: Shu F]] |
| - | [[Category: Shu, F]] | + | [[Category: Stelzer G]] |
| - | [[Category: Stelzer, G]] | + | |
| - | [[Category: H2a/h2b]]
| + | |
| - | [[Category: Histone]]
| + | |
| - | [[Category: Nc2]]
| + | |
| - | [[Category: Negative cofactor]]
| + | |
| - | [[Category: NYSGXRC, New York SGX Research Center for Structural Genomics]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Tata-dna]]
| + | |
| - | [[Category: Tbp]]
| + | |
| - | [[Category: Transcription initiation]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
Function
NC2A_HUMAN The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own.[1] [2]
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
The X-ray structure of a ternary complex of Negative Cofactor 2 (NC2), the TATA box binding protein (TBP), and DNA has been determined at 2.6 A resolution. The N termini of NC2 alpha and beta resemble histones H2A and H2B, respectively, and form a heterodimer that binds to the bent DNA double helix on the underside of the preformed TBP-DNA complex via electrostatic interactions. NC2beta contributes to inhibition of TATA-dependent transcription through interactions of its C-terminal alpha helix with a conserved hydrophobic feature on the upper surface of TBP, which in turn positions the penultimate alpha helix of NC2beta to block recognition of the TBP-DNA complex by transcription factor IIB. Further regulatory implications of the NC2 heterodimer structure are discussed.
Crystal structure of negative cofactor 2 recognizing the TBP-DNA transcription complex.,Kamada K, Shu F, Chen H, Malik S, Stelzer G, Roeder RG, Meisterernst M, Burley SK Cell. 2001 Jul 13;106(1):71-81. PMID:11461703[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Goppelt A, Stelzer G, Lottspeich F, Meisterernst M. A mechanism for repression of class II gene transcription through specific binding of NC2 to TBP-promoter complexes via heterodimeric histone fold domains. EMBO J. 1996 Jun 17;15(12):3105-16. PMID:8670811
- ↑ Mermelstein F, Yeung K, Cao J, Inostroza JA, Erdjument-Bromage H, Eagelson K, Landsman D, Levitt P, Tempst P, Reinberg D. Requirement of a corepressor for Dr1-mediated repression of transcription. Genes Dev. 1996 Apr 15;10(8):1033-48. PMID:8608938
- ↑ Kamada K, Shu F, Chen H, Malik S, Stelzer G, Roeder RG, Meisterernst M, Burley SK. Crystal structure of negative cofactor 2 recognizing the TBP-DNA transcription complex. Cell. 2001 Jul 13;106(1):71-81. PMID:11461703
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