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| | <StructureSection load='4wg0' size='340' side='right'caption='[[4wg0]], [[Resolution|resolution]] 1.82Å' scene=''> | | <StructureSection load='4wg0' size='340' side='right'caption='[[4wg0]], [[Resolution|resolution]] 1.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wg0]] is a 13 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WG0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WG0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wg0]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WG0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=4wg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wg0 OCA], [https://pdbe.org/4wg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wg0 RCSB], [https://www.ebi.ac.uk/pdbsum/4wg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wg0 ProSAT]</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=4wg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wg0 OCA], [http://pdbe.org/4wg0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wg0 RCSB], [http://www.ebi.ac.uk/pdbsum/4wg0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wg0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. | + | [https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref> | + | [https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Rudolph, M G]] | + | [[Category: Rudolph MG]] |
| - | [[Category: Schoch, G]] | + | [[Category: Schoch G]] |
| - | [[Category: Uson, I]] | + | [[Category: Uson I]] |
| - | [[Category: Arcimboldo molecular replacement]]
| + | |
| - | [[Category: Glucocorticoid receptor]]
| + | |
| - | [[Category: Superhelix]]
| + | |
| - | [[Category: Tif2 co-activator peptide]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Disease
NCOA2_HUMAN Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
Function
NCOA2_HUMAN Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.[1]
Publication Abstract from PubMed
Nuclear hormone receptors are cytoplasm-based transcription factors that bind a ligand, translate to the nucleus and initiate gene transcription in complex with a co-activator such as TIF2 (transcriptional intermediary factor 2). For structural studies the co-activator is usually mimicked by a peptide of circa 13 residues, which for the largest part forms an alpha-helix when bound to the receptor. The aim was to co-crystallize the glucocorticoid receptor in complex with a ligand and the TIF2 co-activator peptide. The 1.82 A resolution diffraction data obtained from the crystal could not be phased by molecular replacement using the known receptor structures. HPLC analysis of the crystals revealed the absence of the receptor and indicated that only the co-activator peptide was present. The self-rotation function displayed 13-fold rotational symmetry, which initiated an exhaustive but unsuccessful molecular-replacement approach using motifs of 13-fold symmetry such as alpha- and beta-barrels in various geometries. The structure was ultimately determined by using a single alpha-helix and the software ARCIMBOLDO, which assembles fragments placed by PHASER before using them as seeds for density modification model building in SHELXE. Systematic variation of the helix length revealed upper and lower size limits for successful structure determination. A beautiful but unanticipated structure was obtained that forms superhelices with left-handed twist throughout the crystal, stabilized by ligand interactions. Together with the increasing diversity of structural elements in the Protein Data Bank the results from TIF2 confirm the potential of fragment-based molecular replacement to significantly accelerate the phasing step for native diffraction data at around 2 A resolution.
Structure of a 13-fold superhelix (almost) determined from first principles.,Schoch GA, Sammito M, Millan C, Uson I, Rudolph MG IUCrJ. 2015 Jan 27;2(Pt 2):177-87. doi: 10.1107/S2052252515000238. eCollection, 2015 Mar 1. PMID:25866655[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H. The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J. 1998 Jan 15;17(2):507-19. PMID:9430642 doi:10.1093/emboj/17.2.507
- ↑ Schoch GA, Sammito M, Millan C, Uson I, Rudolph MG. Structure of a 13-fold superhelix (almost) determined from first principles. IUCrJ. 2015 Jan 27;2(Pt 2):177-87. doi: 10.1107/S2052252515000238. eCollection, 2015 Mar 1. PMID:25866655 doi:http://dx.doi.org/10.1107/S2052252515000238
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