6k7w

From Proteopedia

(Difference between revisions)

Current revision

Solution Structure of the CS1 Domain of USP19

Structural highlights

6k7w is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBP19_HUMAN Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked Ubiquitin chains.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Ubiquitin-specific protease 19 (USP19) is a member of the deubiquitinating (DUB) enzymes that catalyze removing the ubiquitin signals from target proteins. Our previous research has demonstrated that USP19 up-regulates the protein level and aggregation of polyQ-expanded huntingtin through the involvement of heat shock protein 90 (HSP90). Here, we present solution structures of the CS1, CS2 and UbL domains of USP19 and structural insights into their domain interactions. We found that the tandem CS domains fold back to interact with the C-terminal USP domain (USPD) intra-molecularly that leads to inhibition of the catalytic core of USP19, especially CS1 interacts with the embedded UbL domain and CS2 does with the CH2 catalytic core. Moreover, CS2 specifically interacts with the NBD domain of HSP90, which can activate the DUB enzyme. A mechanism of auto-inhibition of USP19 and activation by HSP90 is proposed, on which USP19 modulates the protein level of polyQ-expanded huntingtin in cells. This study provides structural and mechanistic insights into the modulation of protein level and aggregation by USP19 with the assistance of HSP90.

Domain interactions reveal auto-inhibition of the deubiquitinating enzyme USP19 and its activation by HSP90 in the modulation of huntingtin aggregation.,Xue W, Zhang SX, He WT, Hong JY, Jiang LL, Hu HY Biochem J. 2020 Nov 13;477(21):4295-4312. doi: 10.1042/BCJ20200536. PMID:33094816^[5]

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

References

↑ Hassink GC, Zhao B, Sompallae R, Altun M, Gastaldello S, Zinin NV, Masucci MG, Lindsten K. The ER-resident ubiquitin-specific protease 19 participates in the UPR and rescues ERAD substrates. EMBO Rep. 2009 Jul;10(7):755-61. Epub 2009 May 22. PMID:19465887 doi:http://dx.doi.org/embor200969
↑ Mei Y, Hahn AA, Hu S, Yang X. The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2. J Biol Chem. 2011 Oct 14;286(41):35380-7. doi: 10.1074/jbc.M111.282020. Epub 2011, Aug 17. PMID:21849505 doi:http://dx.doi.org/10.1074/jbc.M111.282020
↑ Altun M, Zhao B, Velasco K, Liu H, Hassink G, Paschke J, Pereira T, Lindsten K. Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1alpha (HIF-1alpha) during hypoxia. J Biol Chem. 2012 Jan 13;287(3):1962-9. doi: 10.1074/jbc.M111.305615. Epub 2011, Nov 29. PMID:22128162 doi:http://dx.doi.org/10.1074/jbc.M111.305615
↑ Iphofer A, Kummer A, Nimtz M, Ritter A, Arnold T, Frank R, van den Heuvel J, Kessler BM, Jansch L, Franke R. Profiling ubiquitin linkage specificities of deubiquitinating enzymes with branched ubiquitin isopeptide probes. Chembiochem. 2012 Jul 9;13(10):1416-20. doi: 10.1002/cbic.201200261. Epub 2012, Jun 11. PMID:22689415 doi:10.1002/cbic.201200261
↑ Xue W, Zhang SX, He WT, Hong JY, Jiang LL, Hu HY. Domain interactions reveal auto-inhibition of the deubiquitinating enzyme USP19 and its activation by HSP90 in the modulation of huntingtin aggregation. Biochem J. 2020 Nov 13;477(21):4295-4312. doi: 10.1042/BCJ20200536. PMID:33094816 doi:http://dx.doi.org/10.1042/BCJ20200536

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6k7w"

Categories: Homo sapiens | Large Structures | Hu HY | Xue W

@@ Line 1: / Line 1: @@
 ==Solution Structure of the CS1 Domain of USP19==
-<StructureSection load='6k7w' size='340' side='right'caption='[[6k7w]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='6k7w' size='340' side='right'caption='[[6k7w]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6k7w]] 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=6K7W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6K7W FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6k7w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6K7W FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">USP19, KIAA0891, ZMYND9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</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=6k7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k7w OCA], [https://pdbe.org/6k7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6k7w RCSB], [https://www.ebi.ac.uk/pdbsum/6k7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6k7w ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=6k7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k7w OCA], [http://pdbe.org/6k7w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6k7w RCSB], [http://www.ebi.ac.uk/pdbsum/6k7w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6k7w ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/UBP19_HUMAN UBP19_HUMAN]] Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked Ubiquitin chains.<ref>PMID:19465887</ref> <ref>PMID:21849505</ref> <ref>PMID:22128162</ref> <ref>PMID:22689415</ref>
+[https://www.uniprot.org/uniprot/UBP19_HUMAN UBP19_HUMAN] Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked Ubiquitin chains.<ref>PMID:19465887</ref> <ref>PMID:21849505</ref> <ref>PMID:22128162</ref> <ref>PMID:22689415</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ubiquitinyl hydrolase 1]]
+[[Category: Hu HY]]
-[[Category: Hu, H Y]]
+[[Category: Xue W]]
-[[Category: Xue, W]]
-[[Category: Autoinhibitory regulation]]
-[[Category: Cs domain]]
-[[Category: Hydrolase inhibitor]]

6k7w

From Proteopedia

Current revision

Solution Structure of the CS1 Domain of USP19

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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