View source for 2kmk


==Gfi-1 Zinc Fingers 3-5 complexed with DNA==
<StructureSection load='2kmk' size='340' side='right'caption='[[2kmk]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kmk]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KMK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KMK 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=2kmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kmk OCA], [https://pdbe.org/2kmk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kmk RCSB], [https://www.ebi.ac.uk/pdbsum/2kmk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kmk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GFI1_RAT GFI1_RAT] Transcription repressor essential for hematopoiesis. Functions in a cell-context and development-specific manner. Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes. Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development. Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling. Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA. Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth. Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 promoter region. Implicated in the maintenance of inner ear hair cells (By similarity).<ref>PMID:20190815</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/2kmk_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kmk ConSurf].
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== Publication Abstract from PubMed ==
Gfi-1 is a crucial transcriptional repressor for the precise regulation of cell proliferation and differentiation in hematopoiesis. Recently, this protein has also been demonstrated to be capable of restricting the proliferation of hematopoietic stem cells, a process that appears to be vital for the long-term competency of hematopoietic stem cells. These two seemingly opposite outcomes of regulation are likely to arise from its interactions with a variety of cellular partners. Such interactions can directly affect the genes that Gfi-1 recognizes through its DNA binding zinc-finger domain. In this work, we report the determination of the solution structure of Gfi-1 zinc fingers 3-5 in complex with a 16-mer consensus DNA using multidimensional NMR method. Unlike a proposed minor-groove binding model based on methylation interference experiments, our structure clearly shows that Gfi-1 zinc fingers 3-5 bind into the major groove of the target DNA reminiscent of canonical C(2)H(2) zinc-finger domains. The fourth and fifth zinc fingers recognize the AATC core sequence by forming base-specific hydrogen bonds between the side chains of Asn382, Gln379, and Asp354 and the bases of the invariant adenines and cytosine. Overall, the current work provides valuable insight into the structural determinants for DNA binding specificity, in particular for the TCA triplet that has not been observed in any other structures of zinc finger-DNA complexes, as well as molecular rationales for a naturally occurring mutation that causes acute myeloid leukemia.

Solution structure of Gfi-1 zinc domain bound to consensus DNA.,Lee S, Doddapaneni K, Hogue A, McGhee L, Meyers S, Wu Z J Mol Biol. 2010 Apr 9;397(4):1055-66. Epub 2010 Feb 11. PMID:20153336<ref>PMID:20153336</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Lee S]]
[[Category: Wu Z]]