6qu1

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the KAP1 RBCC domain in complex with the SMARCAD1 CUE1 domain at 3.7 angstrom resolution.

Structural highlights

6qu1 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TIF1B_HUMAN Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17]

Publication Abstract from PubMed

Ubiquitylation, the posttranslational linkage of ubiquitin moieties to lysines in target proteins, helps regulate a myriad of biological processes. Ubiquitin, and sometimes ubiquitin-homology domains, are recognized by ubiquitin-binding domains, including CUE domains. CUE domains are thus generally thought to function by mediating interactions with ubiquitylated proteins. The chromatin remodeler, SMARCAD1, interacts with KAP1, a transcriptional corepressor. The SMARCAD1-KAP1 interaction is direct and involves the first SMARCAD1 CUE domain (CUE1) and the RBCC domain of KAP1. Here, we present a structural model of the KAP1 RBCC-SMARCAD1 CUE1 complex based on X-ray crystallography. Remarkably, CUE1, a canonical CUE domain, recognizes a cluster of exposed hydrophobic and surrounding charged/amphipathic residues on KAP1, which are presented in the context of a coiled-coil domain, not in a structure resembling ubiquitin. Together, these data suggest that CUE domains may have a wider function than simply recognizing ubiquitin and the ubiquitin-fold.

A Ubiquitin-Binding Domain that Binds a Structural Fold Distinct from that of Ubiquitin.,Lim M, Newman JA, Williams HL, Masino L, Aitkenhead H, Gravard AE, Gileadi O, Svejstrup JQ Structure. 2019 May 28. pii: S0969-2126(19)30165-0. doi:, 10.1016/j.str.2019.05.003. PMID:31204252^[18]

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

References

↑ Friedman JR, Fredericks WJ, Jensen DE, Speicher DW, Huang XP, Neilson EG, Rauscher FJ 3rd. KAP-1, a novel corepressor for the highly conserved KRAB repression domain. Genes Dev. 1996 Aug 15;10(16):2067-78. PMID:8769649
↑ Moosmann P, Georgiev O, Le Douarin B, Bourquin JP, Schaffner W. Transcriptional repression by RING finger protein TIF1 beta that interacts with the KRAB repressor domain of KOX1. Nucleic Acids Res. 1996 Dec 15;24(24):4859-67. PMID:9016654
↑ Agata Y, Matsuda E, Shimizu A. Two novel Kruppel-associated box-containing zinc-finger proteins, KRAZ1 and KRAZ2, repress transcription through functional interaction with the corepressor KAP-1 (TIF1beta/KRIP-1). J Biol Chem. 1999 Jun 4;274(23):16412-22. PMID:10347202
↑ Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ 3rd. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 2002 Apr 15;16(8):919-32. PMID:11959841 doi:http://dx.doi.org/10.1101/gad.973302
↑ Lechner MS, Schultz DC, Negorev D, Maul GG, Rauscher FJ 3rd. The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain. Biochem Biophys Res Commun. 2005 Jun 17;331(4):929-37. PMID:15882967 doi:http://dx.doi.org/10.1016/j.bbrc.2005.04.016
↑ Wang C, Ivanov A, Chen L, Fredericks WJ, Seto E, Rauscher FJ 3rd, Chen J. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. EMBO J. 2005 Sep 21;24(18):3279-90. Epub 2005 Aug 18. PMID:16107876 doi:http://dx.doi.org/10.1038/sj.emboj.7600791
↑ White DE, Negorev D, Peng H, Ivanov AV, Maul GG, Rauscher FJ 3rd. KAP1, a novel substrate for PIKK family members, colocalizes with numerous damage response factors at DNA lesions. Cancer Res. 2006 Dec 15;66(24):11594-9. PMID:17178852 doi:http://dx.doi.org/10.1158/0008-5472.CAN-06-4138
↑ Ziv Y, Bielopolski D, Galanty Y, Lukas C, Taya Y, Schultz DC, Lukas J, Bekker-Jensen S, Bartek J, Shiloh Y. Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat Cell Biol. 2006 Aug;8(8):870-6. Epub 2006 Jul 23. PMID:16862143 doi:http://dx.doi.org/10.1038/ncb1446
↑ Lee YK, Thomas SN, Yang AJ, Ann DK. Doxorubicin down-regulates Kruppel-associated box domain-associated protein 1 sumoylation that relieves its transcription repression on p21WAF1/CIP1 in breast cancer MCF-7 cells. J Biol Chem. 2007 Jan 19;282(3):1595-606. Epub 2006 Nov 1. PMID:17079232 doi:http://dx.doi.org/10.1074/jbc.M606306200
↑ Wang C, Rauscher FJ 3rd, Cress WD, Chen J. Regulation of E2F1 function by the nuclear corepressor KAP1. J Biol Chem. 2007 Oct 12;282(41):29902-9. Epub 2007 Aug 17. PMID:17704056 doi:10.1074/jbc.M704757200
↑ Li X, Lee YK, Jeng JC, Yen Y, Schultz DC, Shih HM, Ann DK. Role for KAP1 serine 824 phosphorylation and sumoylation/desumoylation switch in regulating KAP1-mediated transcriptional repression. J Biol Chem. 2007 Dec 14;282(50):36177-89. Epub 2007 Oct 17. PMID:17942393 doi:http://dx.doi.org/10.1074/jbc.M706912200
↑ Ivanov AV, Peng H, Yurchenko V, Yap KL, Negorev DG, Schultz DC, Psulkowski E, Fredericks WJ, White DE, Maul GG, Sadofsky MJ, Zhou MM, Rauscher FJ 3rd. PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. Mol Cell. 2007 Dec 14;28(5):823-37. PMID:18082607 doi:http://dx.doi.org/10.1016/j.molcel.2007.11.012
↑ Suzuki C, Murakumo Y, Kawase Y, Sato T, Morinaga T, Fukuda N, Enomoto A, Ichihara M, Takahashi M. A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1. Biochem Biophys Res Commun. 2008 Feb 1;366(1):226-32. Epub 2007 Dec 3. PMID:18060868 doi:http://dx.doi.org/S0006-291X(07)02541-7
↑ Gilmore-Hebert M, Ramabhadran R, Stern DF. Interactions of ErbB4 and Kap1 connect the growth factor and DNA damage response pathways. Mol Cancer Res. 2010 Oct;8(10):1388-98. doi: 10.1158/1541-7786.MCR-10-0042. Epub , 2010 Sep 21. PMID:20858735 doi:10.1158/1541-7786.MCR-10-0042
↑ Doyle JM, Gao J, Wang J, Yang M, Potts PR. MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases. Mol Cell. 2010 Sep 24;39(6):963-74. PMID:20864041 doi:10.1016/j.molcel.2010.08.029
↑ Li X, Lin HH, Chen H, Xu X, Shih HM, Ann DK. SUMOylation of the transcriptional co-repressor KAP1 is regulated by the serine and threonine phosphatase PP1. Sci Signal. 2010 Apr 27;3(119):ra32. doi: 10.1126/scisignal.2000781. PMID:20424263 doi:http://dx.doi.org/10.1126/scisignal.2000781
↑ Liang Q, Deng H, Li X, Wu X, Tang Q, Chang TH, Peng H, Rauscher FJ 3rd, Ozato K, Zhu F. Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7. J Immunol. 2011 Nov 1;187(9):4754-63. doi: 10.4049/jimmunol.1101704. Epub 2011, Sep 21. PMID:21940674 doi:http://dx.doi.org/10.4049/jimmunol.1101704
↑ Lim M, Newman JA, Williams HL, Masino L, Aitkenhead H, Gravard AE, Gileadi O, Svejstrup JQ. A Ubiquitin-Binding Domain that Binds a Structural Fold Distinct from that of Ubiquitin. Structure. 2019 May 28. pii: S0969-2126(19)30165-0. doi:, 10.1016/j.str.2019.05.003. PMID:31204252 doi:http://dx.doi.org/10.1016/j.str.2019.05.003

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/6qu1"

@@ Line 3: / Line 3: @@
 <StructureSection load='6qu1' size='340' side='right'caption='[[6qu1]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6qu1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QU1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QU1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6qu1]] is a 2 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=6QU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QU1 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 3.7&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qu1 OCA], [http://pdbe.org/6qu1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qu1 RCSB], [http://www.ebi.ac.uk/pdbsum/6qu1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qu1 ProSAT]</span></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=6qu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qu1 OCA], [https://pdbe.org/6qu1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qu1 RCSB], [https://www.ebi.ac.uk/pdbsum/6qu1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qu1 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/SMRCD_HUMAN SMRCD_HUMAN]] Huriez syndrome;Isolated congenital adermatoglyphia;Absence of fingerprints-congenital milia syndrome. The disease is caused by mutations affecting the gene represented in this entry. Splice site mutations causing aberrant splicing of skin-specific isoform 3 are likely to exert a loss-of-function effect and are involved in ADERM.<ref>PMID:21820097</ref> <ref>PMID:24909267</ref>   The disease is caused by mutations affecting the gene represented in this entry. Splice site mutations causing aberrant splicing of skin-specific isoform 3 are likely to exert a loss-of-function effect and are involved in BSNS.<ref>PMID:24664640</ref> <ref>PMID:26932190</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/TIF1B_HUMAN TIF1B_HUMAN]] Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6.<ref>PMID:8769649</ref> <ref>PMID:9016654</ref> <ref>PMID:10347202</ref> <ref>PMID:11959841</ref> <ref>PMID:15882967</ref> <ref>PMID:16107876</ref> <ref>PMID:17178852</ref> <ref>PMID:16862143</ref> <ref>PMID:17079232</ref> <ref>PMID:17704056</ref> <ref>PMID:17942393</ref> <ref>PMID:18082607</ref> <ref>PMID:18060868</ref> <ref>PMID:20858735</ref> <ref>PMID:20864041</ref> <ref>PMID:20424263</ref> <ref>PMID:21940674</ref>  [[http://www.uniprot.org/uniprot/SMRCD_HUMAN SMRCD_HUMAN]] DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing.<ref>PMID:21549307</ref> <ref>PMID:22960744</ref>
+[https://www.uniprot.org/uniprot/TIF1B_HUMAN TIF1B_HUMAN] Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6.<ref>PMID:8769649</ref> <ref>PMID:9016654</ref> <ref>PMID:10347202</ref> <ref>PMID:11959841</ref> <ref>PMID:15882967</ref> <ref>PMID:16107876</ref> <ref>PMID:17178852</ref> <ref>PMID:16862143</ref> <ref>PMID:17079232</ref> <ref>PMID:17704056</ref> <ref>PMID:17942393</ref> <ref>PMID:18082607</ref> <ref>PMID:18060868</ref> <ref>PMID:20858735</ref> <ref>PMID:20864041</ref> <ref>PMID:20424263</ref> <ref>PMID:21940674</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: DNA helicase]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Aitkenhead, H]]
+[[Category: Aitkenhead H]]
-[[Category: Arrowsmith, C H]]
+[[Category: Arrowsmith CH]]
-[[Category: Bountra, C]]
+[[Category: Bountra C]]
-[[Category: Delft, F von]]
+[[Category: Edwards A]]
-[[Category: Edwards, A]]
+[[Category: Gavard A]]
-[[Category: Gavard, A]]
+[[Category: Gileadi O]]
-[[Category: Gileadi, O]]
+[[Category: Lim M]]
-[[Category: Lim, M]]
+[[Category: Newman JA]]
-[[Category: Newman, J A]]
+[[Category: Svejstrup JQ]]
-[[Category: Svejstrup, J Q]]
+[[Category: Williams HL]]
-[[Category: Williams, H L]]
+[[Category: Von Delft F]]
-[[Category: Cue domain]]
-[[Category: Ligase]]
-[[Category: Transcriptional co-repressor]]
-[[Category: Trim28]]
-[[Category: Ubuiquitin]]

6qu1

From Proteopedia

Current revision

Crystal structure of the KAP1 RBCC domain in complex with the SMARCAD1 CUE1 domain at 3.7 angstrom resolution.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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