2com

From Proteopedia

(Difference between revisions)

Revision as of 08:29, 23 May 2018

The solution structure of the SWIRM domain of human LSD1

Structural highlights

2com is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	LSD1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Function

[KDM1A_HUMAN] Histone demethylase that demethylates both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development.^[1] ^[2] ^[3] ^[4] ^[5]

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

SWIRM is an evolutionarily conserved domain involved in several chromatin-modifying complexes. Recently, the LSD1 protein, which bears a SWIRM domain, was found to be a demethylase for Lys4-methylated histone H3. Here, we report a solution structure of the SWIRM domain of human LSD1. It forms a compact fold composed of 6 alpha helices, in which a 20 amino acid long helix (alpha4) is surrounded by 5 other short helices. The SWIRM domain structure could be divided into the N-terminal part (alpha1-alpha3) and the C-terminal part (alpha4-alpha6), which are connected to each other by a salt bridge. While the N-terminal part forms a SWIRM-specific structure, the C-terminal part adopts a helix-turn-helix (HTH)-related fold. We discuss a model in which the SWIRM domain acts as an anchor site for a histone tail.

Solution structure of the SWIRM domain of human histone demethylase LSD1.,Tochio N, Umehara T, Koshiba S, Inoue M, Yabuki T, Aoki M, Seki E, Watanabe S, Tomo Y, Hanada M, Ikari M, Sato M, Terada T, Nagase T, Ohara O, Shirouzu M, Tanaka A, Kigawa T, Yokoyama S Structure. 2006 Mar;14(3):457-68. PMID:16531230^[6]

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

References

↑ Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G, Shiekhattar R. A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7420-5. PMID:12032298 doi:10.1073/pnas.112008599
↑ Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004 Dec 29;119(7):941-53. PMID:15620353 doi:http://dx.doi.org/10.1016/j.cell.2004.12.012
↑ Metzger E, Wissmann M, Yin N, Muller JM, Schneider R, Peters AH, Gunther T, Buettner R, Schule R. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature. 2005 Sep 15;437(7057):436-9. Epub 2005 Aug 3. PMID:16079795 doi:http://dx.doi.org/10.1038/nature04020
↑ Huang J, Sengupta R, Espejo AB, Lee MG, Dorsey JA, Richter M, Opravil S, Shiekhattar R, Bedford MT, Jenuwein T, Berger SL. p53 is regulated by the lysine demethylase LSD1. Nature. 2007 Sep 6;449(7158):105-8. PMID:17805299 doi:nature06092
↑ Metzger E, Imhof A, Patel D, Kahl P, Hoffmeyer K, Friedrichs N, Muller JM, Greschik H, Kirfel J, Ji S, Kunowska N, Beisenherz-Huss C, Gunther T, Buettner R, Schule R. Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4. Nature. 2010 Apr 1;464(7289):792-6. doi: 10.1038/nature08839. Epub 2010 Mar 14. PMID:20228790 doi:http://dx.doi.org/10.1038/nature08839
↑ Tochio N, Umehara T, Koshiba S, Inoue M, Yabuki T, Aoki M, Seki E, Watanabe S, Tomo Y, Hanada M, Ikari M, Sato M, Terada T, Nagase T, Ohara O, Shirouzu M, Tanaka A, Kigawa T, Yokoyama S. Solution structure of the SWIRM domain of human histone demethylase LSD1. Structure. 2006 Mar;14(3):457-68. PMID:16531230 doi:10.1016/j.str.2005.12.004

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2com"

@@ Line 1: / Line 1: @@
 ==The solution structure of the SWIRM domain of human LSD1==
 <StructureSection load='2com' size='340' side='right' caption='[[2com]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2com]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2COM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2COM FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LSD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2com FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2com OCA], [http://pdbe.org/2com PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2com RCSB], [http://www.ebi.ac.uk/pdbsum/2com PDBsum], [http://www.topsan.org/Proteins/RSGI/2com TOPSAN]</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=2com FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2com OCA], [http://pdbe.org/2com PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2com RCSB], [http://www.ebi.ac.uk/pdbsum/2com PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2com ProSAT], [http://www.topsan.org/Proteins/RSGI/2com TOPSAN]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/co/2com_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/co/2com_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2com

From Proteopedia

Revision as of 08:29, 23 May 2018

The solution structure of the SWIRM domain of human LSD1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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