6v2r

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of chromodomain of CBX7 mutant V13A in complex with inhibitor UNC3866

Structural highlights

6v2r is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CBX7_HUMAN Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Promotes histone H3 trimethylation at 'Lys-9' (H3K9me3). Binds to trimethylated lysine residues in histones, and possibly also other proteins. Regulator of cellular lifespan by maintaining the repression of CDKN2A, but not by inducing telomerase activity.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The CDY (chromodomain on the Y) proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize the lysine-methylated ARKS motif embedded in histone and non-histone proteins. Interestingly, the CDY chromodomains exhibit different binding preferences for the lysine-methylated ARKS motif in different sequence contexts. Here, we present the structural basis for selective binding of CDY1 to H3K9me3 and preferential binding of CDYL2 to H3tK27me3 over H3K27me3. In addition, we use a CDYL1/2-selective compound, UNC4850, to gain further insight into the molecular mechanisms underlying CDYL2 binding specificity. Our work also provides critical implications that CDYL1b's role in the regulation of neural development is dependent on its recognition of the lysine-methylated ARKS motif.

Structural Basis for the Binding Selectivity of Human CDY Chromodomains.,Dong C, Liu Y, Lyu TJ, Beldar S, Lamb KN, Tempel W, Li Y, Li Z, James LI, Qin S, Wang Y, Min J Cell Chem Biol. 2020 May 26. pii: S2451-9456(20)30153-7. doi:, 10.1016/j.chembiol.2020.05.007. PMID:32470319^[5]

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

References

↑ Maertens GN, El Messaoudi-Aubert S, Racek T, Stock JK, Nicholls J, Rodriguez-Niedenfuhr M, Gil J, Peters G. Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus. PLoS One. 2009 Jul 28;4(7):e6380. doi: 10.1371/journal.pone.0006380. PMID:19636380 doi:http://dx.doi.org/10.1371/journal.pone.0006380
↑ Li Q, Wang X, Lu Z, Zhang B, Guan Z, Liu Z, Zhong Q, Gu L, Zhou J, Zhu B, Ji J, Deng D. Polycomb CBX7 directly controls trimethylation of histone H3 at lysine 9 at the p16 locus. PLoS One. 2010 Oct 29;5(10):e13732. doi: 10.1371/journal.pone.0013732. PMID:21060834 doi:http://dx.doi.org/10.1371/journal.pone.0013732
↑ Vandamme J, Volkel P, Rosnoblet C, Le Faou P, Angrand PO. Interaction proteomics analysis of polycomb proteins defines distinct PRC1 complexes in mammalian cells. Mol Cell Proteomics. 2011 Apr;10(4):M110.002642. doi: 10.1074/mcp.M110.002642., Epub 2011 Jan 31. PMID:21282530 doi:10.1074/mcp.M110.002642
↑ Kaustov L, Ouyang H, Amaya M, Lemak A, Nady N, Duan S, Wasney GA, Li Z, Vedadi M, Schapira M, Min J, Arrowsmith CH. Recognition and specificity determinants of the human cbx chromodomains. J Biol Chem. 2011 Jan 7;286(1):521-9. Epub 2010 Nov 3. PMID:21047797 doi:10.1074/jbc.M110.191411
↑ Dong C, Liu Y, Lyu TJ, Beldar S, Lamb KN, Tempel W, Li Y, Li Z, James LI, Qin S, Wang Y, Min J. Structural Basis for the Binding Selectivity of Human CDY Chromodomains. Cell Chem Biol. 2020 May 26. pii: S2451-9456(20)30153-7. doi:, 10.1016/j.chembiol.2020.05.007. PMID:32470319 doi:http://dx.doi.org/10.1016/j.chembiol.2020.05.007

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6v2r"

@@ Line 3: / Line 3: @@
 <StructureSection load='6v2r' size='340' side='right'caption='[[6v2r]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6v2r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V2R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V2R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6v2r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V2R FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></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]] 1.6&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5R0:4-~{TERT}-BUTYLBENZOIC+ACID'>5R0</scene>, <scene name='pdbligand=5R5:METHYL+(2~{S})-2-AZANYL-3-OXIDANYL-PROPANOATE'>5R5</scene>, <scene name='pdbligand=ELY:N~6~,N~6~-DIETHYL-L-LYSINE'>ELY</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5R0:4-~{TERT}-BUTYLBENZOIC+ACID'>5R0</scene>, <scene name='pdbligand=5R5:METHYL+(2~{S})-2-AZANYL-3-OXIDANYL-PROPANOATE'>5R5</scene>, <scene name='pdbligand=ELY:N~6~,N~6~-DIETHYL-L-LYSINE'>ELY</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CBX7 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6v2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v2r OCA], [https://pdbe.org/6v2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v2r RCSB], [https://www.ebi.ac.uk/pdbsum/6v2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v2r ProSAT]</span></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=6v2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v2r OCA], [http://pdbe.org/6v2r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v2r RCSB], [http://www.ebi.ac.uk/pdbsum/6v2r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v2r ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CBX7_HUMAN CBX7_HUMAN]] Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Promotes histone H3 trimethylation at 'Lys-9' (H3K9me3). Binds to trimethylated lysine residues in histones, and possibly also other proteins. Regulator of cellular lifespan by maintaining the repression of CDKN2A, but not by inducing telomerase activity.<ref>PMID:19636380</ref> <ref>PMID:21060834</ref> <ref>PMID:21282530</ref> <ref>PMID:21047797</ref>
+[https://www.uniprot.org/uniprot/CBX7_HUMAN CBX7_HUMAN] Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Promotes histone H3 trimethylation at 'Lys-9' (H3K9me3). Binds to trimethylated lysine residues in histones, and possibly also other proteins. Regulator of cellular lifespan by maintaining the repression of CDKN2A, but not by inducing telomerase activity.<ref>PMID:19636380</ref> <ref>PMID:21060834</ref> <ref>PMID:21282530</ref> <ref>PMID:21047797</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Arrowsmith, C H]]
+[[Category: Synthetic construct]]
-[[Category: Bountra, C]]
+[[Category: Arrowsmith CH]]
-[[Category: Dickson, B M]]
+[[Category: Bountra C]]
-[[Category: Edwards, A M]]
+[[Category: Dickson BM]]
-[[Category: Frye, S V]]
+[[Category: Edwards AM]]
-[[Category: James, L I]]
+[[Category: Frye SV]]
-[[Category: Liu, Y]]
+[[Category: James LI]]
-[[Category: Min, J]]
+[[Category: Liu Y]]
-[[Category: Structural genomic]]
+[[Category: Min J]]
-[[Category: Stuckey, J I]]
+[[Category: Stuckey JI]]
-[[Category: Tempel, W]]
+[[Category: Tempel W]]
-[[Category: Walker, J R]]
+[[Category: Walker JR]]
-[[Category: Gene regulation]]
-[[Category: Sgc]]

6v2r

From Proteopedia

Current revision

Crystal Structure of chromodomain of CBX7 mutant V13A in complex with inhibitor UNC3866

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox