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| - | [[Image:1liq.gif|left|200px]]<br /> | |
| - | <applet load="1liq" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1liq" /> | |
| - | '''Non-native Solution Structure of a fragment of the CH1 domain of CBP'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Non-native Solution Structure of a fragment of the CH1 domain of CBP== |
| - | Many different zinc binding modules have been identified. Their abundance, and variety suggests that the formation of zinc binding folds might be, relatively common. We have determined the structure of CH1(1), a, 27-residue peptide derived from the first cysteine/histidine-rich region, (CH1) of CREB binding protein (CBP). This peptide forms a highly ordered, zinc-dependent fold that is distinct from known folds. The structure, differs from a subsequently determined structure of a larger region from, the CH3 region of CBP, and the CH1(1) fold probably represents a, nonphysiologically active form. Despite this, the fold is thermostable and, tolerant to both multiple alanine mutations and changes in the zinc-ligand, spacing. Our data support the idea that zinc binding domains may arise, frequently. Additionally, such structures may prove useful as scaffolds, for protein design, given their stability and robustness. | + | <StructureSection load='1liq' size='340' side='right'caption='[[1liq]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1liq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LIQ FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=1liq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1liq OCA], [https://pdbe.org/1liq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1liq RCSB], [https://www.ebi.ac.uk/pdbsum/1liq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1liq ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:[https://omim.org/entry/180849 180849]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.<ref>PMID:11331617</ref> <ref>PMID:12114483</ref> <ref>PMID:12566391</ref> <ref>PMID:15706485</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Many different zinc binding modules have been identified. Their abundance and variety suggests that the formation of zinc binding folds might be relatively common. We have determined the structure of CH1(1), a 27-residue peptide derived from the first cysteine/histidine-rich region (CH1) of CREB binding protein (CBP). This peptide forms a highly ordered zinc-dependent fold that is distinct from known folds. The structure differs from a subsequently determined structure of a larger region from the CH3 region of CBP, and the CH1(1) fold probably represents a nonphysiologically active form. Despite this, the fold is thermostable and tolerant to both multiple alanine mutations and changes in the zinc-ligand spacing. Our data support the idea that zinc binding domains may arise frequently. Additionally, such structures may prove useful as scaffolds for protein design, given their stability and robustness. |
| | | | |
| - | ==Disease==
| + | A new zinc binding fold underlines the versatility of zinc binding modules in protein evolution.,Sharpe BK, Matthews JM, Kwan AH, Newton A, Gell DA, Crossley M, Mackay JP Structure. 2002 May;10(5):639-48. PMID:12015147<ref>PMID:12015147</ref> |
| - | Known diseases associated with this structure: Blue-cone monochromacy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=303900 303900]], Colorblindness, protan OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=303900 303900]], Rubenstein-Taybi syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600140 600140]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1LIQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LIQ OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1liq" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | A new zinc binding fold underlines the versatility of zinc binding modules in protein evolution., Sharpe BK, Matthews JM, Kwan AH, Newton A, Gell DA, Crossley M, Mackay JP, Structure. 2002 May;10(5):639-48. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12015147 12015147]
| + | *[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]] |
| - | [[Category: Single protein]] | + | == References == |
| - | [[Category: Crossley, M.]] | + | <references/> |
| - | [[Category: Gell, D.A.]] | + | __TOC__ |
| - | [[Category: Kwan, A.H.Y.]] | + | </StructureSection> |
| - | [[Category: Mackay, J.P.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Matthews, J.M.]] | + | [[Category: Large Structures]] |
| - | [[Category: Newton, A.]] | + | [[Category: Crossley M]] |
| - | [[Category: Sharpe, B.K.]] | + | [[Category: Gell DA]] |
| - | [[Category: ZN]]
| + | [[Category: Kwan AHY]] |
| - | [[Category: protein design]]
| + | [[Category: Mackay JP]] |
| - | [[Category: zinc finger]]
| + | [[Category: Matthews JM]] |
| - | | + | [[Category: Newton A]] |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:01:31 2007''
| + | [[Category: Sharpe BK]] |
| Structural highlights
Disease
CBP_HUMAN Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:180849. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.[1] [2] [3] [4]
Function
CBP_HUMAN Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.[5] [6] [7] [8]
Publication Abstract from PubMed
Many different zinc binding modules have been identified. Their abundance and variety suggests that the formation of zinc binding folds might be relatively common. We have determined the structure of CH1(1), a 27-residue peptide derived from the first cysteine/histidine-rich region (CH1) of CREB binding protein (CBP). This peptide forms a highly ordered zinc-dependent fold that is distinct from known folds. The structure differs from a subsequently determined structure of a larger region from the CH3 region of CBP, and the CH1(1) fold probably represents a nonphysiologically active form. Despite this, the fold is thermostable and tolerant to both multiple alanine mutations and changes in the zinc-ligand spacing. Our data support the idea that zinc binding domains may arise frequently. Additionally, such structures may prove useful as scaffolds for protein design, given their stability and robustness.
A new zinc binding fold underlines the versatility of zinc binding modules in protein evolution.,Sharpe BK, Matthews JM, Kwan AH, Newton A, Gell DA, Crossley M, Mackay JP Structure. 2002 May;10(5):639-48. PMID:12015147[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Murata T, Kurokawa R, Krones A, Tatsumi K, Ishii M, Taki T, Masuno M, Ohashi H, Yanagisawa M, Rosenfeld MG, Glass CK, Hayashi Y. Defect of histone acetyltransferase activity of the nuclear transcriptional coactivator CBP in Rubinstein-Taybi syndrome. Hum Mol Genet. 2001 May 1;10(10):1071-6. PMID:11331617
- ↑ Bartsch O, Locher K, Meinecke P, Kress W, Seemanova E, Wagner A, Ostermann K, Rodel G. Molecular studies in 10 cases of Rubinstein-Taybi syndrome, including a mild variant showing a missense mutation in codon 1175 of CREBBP. J Med Genet. 2002 Jul;39(7):496-501. PMID:12114483
- ↑ Kalkhoven E, Roelfsema JH, Teunissen H, den Boer A, Ariyurek Y, Zantema A, Breuning MH, Hennekam RC, Peters DJ. Loss of CBP acetyltransferase activity by PHD finger mutations in Rubinstein-Taybi syndrome. Hum Mol Genet. 2003 Feb 15;12(4):441-50. PMID:12566391
- ↑ Roelfsema JH, White SJ, Ariyurek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, den Dunnen JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet. 2005 Apr;76(4):572-80. Epub 2005 Feb 10. PMID:15706485 doi:S0002-9297(07)62869-9
- ↑ Zhang W, Bieker JJ. Acetylation and modulation of erythroid Kruppel-like factor (EKLF) activity by interaction with histone acetyltransferases. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9855-60. PMID:9707565
- ↑ Hung HL, Kim AY, Hong W, Rakowski C, Blobel GA. Stimulation of NF-E2 DNA binding by CREB-binding protein (CBP)-mediated acetylation. J Biol Chem. 2001 Apr 6;276(14):10715-21. Epub 2001 Jan 11. PMID:11154691 doi:10.1074/jbc.M007846200
- ↑ Masumi A, Yamakawa Y, Fukazawa H, Ozato K, Komuro K. Interferon regulatory factor-2 regulates cell growth through its acetylation. J Biol Chem. 2003 Jul 11;278(28):25401-7. Epub 2003 May 7. PMID:12738767 doi:10.1074/jbc.M213037200
- ↑ Iioka T, Furukawa K, Yamaguchi A, Shindo H, Yamashita S, Tsukazaki T. P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain. J Bone Miner Res. 2003 Aug;18(8):1419-29. PMID:12929931 doi:http://dx.doi.org/10.1359/jbmr.2003.18.8.1419
- ↑ Sharpe BK, Matthews JM, Kwan AH, Newton A, Gell DA, Crossley M, Mackay JP. A new zinc binding fold underlines the versatility of zinc binding modules in protein evolution. Structure. 2002 May;10(5):639-48. PMID:12015147
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