6kcz

From Proteopedia

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Revision as of 05:44, 21 August 2019

Solution structure of the ZnF-UBP domain of USP20/VDU2

Structural highlights

6kcz is a 1 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 5z4i. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	USP20, KIAA1003, LSFR3A, VDU2 (HUMAN)
Activity:	Ubiquitinyl hydrolase 1, with EC number 3.4.19.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBP20_HUMAN] Deubiquitinating enzyme involved in beta-2 adrenergic receptor (ADRB2) recycling. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Deubiquitinase USP20/VDU2 has been demonstrated to play important roles in multiple cellular processes by controlling the life span of substrate proteins including hypoxia-inducible factor HIF1alpha, and so forth. USP20 contains four distinct structural domains including the N-terminal zinc-finger ubiquitin binding domain (ZnF-UBP), the catalytic domain (USP domain), and two tandem DUSP domains, and none of the structures for these four domains has been solved. Meanwhile, except for the ZnF-UBP domain, the biological functions for USP20's catalytic domain and tandem DUSP domains have been at least partially clarified. Here in this study, we determined the solution structure of USP20 ZnF-UBP domain and investigated its binding properties with mono-ubiquitin and poly-ubiquitin (K48-linked di-ubiquitin) by using NMR and molecular modeling techniques. USP20's ZnF-UBP domain forms a spherically shaped fold consisting of a central beta-sheet with either one alpha-helix or two alpha-helices packed on each side of the sheet. However, although having formed a canonical core structure essential for ubiquitin recognition, USP20 ZnF-UBP presents weak ubiquitin binding capacity. The structural basis for understanding USP20 ZnF-UBP's ubiquitin binding capacity was revealed by NMR data-driven docking. Although the electrostatic interactions between D264 of USP5 (E87 in USP20 ZnF-UBP) and R74 of ubiquitin are kept, the loss of the extensive interactions formed between ubiquitin's di-glycine motif and the conserved and non-conserved residues of USP20 ZnF-UBP domain (W41, E55, and Y84) causes a significant decrease in its binding affinity to ubiquitin. Our findings indicate that USP20 ZnF-UBP domain might have a physiological role unrelated to its ubiquitin binding capacity.

Structural and functional studies of USP20 ZnF-UBP domain by NMR.,Yang Y, Ding Y, Zhou C, Wen Y, Zhang N Protein Sci. 2019 Sep;28(9):1606-1619. doi: 10.1002/pro.3675. Epub 2019 Aug 9. PMID:31278784^[5]

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

References

↑ Li Z, Wang D, Na X, Schoen SR, Messing EM, Wu G. Identification of a deubiquitinating enzyme subfamily as substrates of the von Hippel-Lindau tumor suppressor. Biochem Biophys Res Commun. 2002 Jun 14;294(3):700-9. PMID:12056827 doi:http://dx.doi.org/10.1016/S0006-291X(02)00534-X
↑ Curcio-Morelli C, Zavacki AM, Christofollete M, Gereben B, de Freitas BC, Harney JW, Li Z, Wu G, Bianco AC. Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation. J Clin Invest. 2003 Jul;112(2):189-96. doi: 10.1172/JCI18348. PMID:12865408 doi:http://dx.doi.org/10.1172/JCI18348
↑ Li Z, Wang D, Messing EM, Wu G. VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1alpha. EMBO Rep. 2005 Apr;6(4):373-8. doi: 10.1038/sj.embor.7400377. PMID:15776016 doi:http://dx.doi.org/10.1038/sj.embor.7400377
↑ Berthouze M, Venkataramanan V, Li Y, Shenoy SK. The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. EMBO J. 2009 Jun 17;28(12):1684-96. doi: 10.1038/emboj.2009.128. Epub 2009 May 7. PMID:19424180 doi:http://dx.doi.org/10.1038/emboj.2009.128
↑ Yang Y, Ding Y, Zhou C, Wen Y, Zhang N. Structural and functional studies of USP20 ZnF-UBP domain by NMR. Protein Sci. 2019 Sep;28(9):1606-1619. doi: 10.1002/pro.3675. Epub 2019 Aug 9. PMID:31278784 doi:http://dx.doi.org/10.1002/pro.3675

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/6kcz"

@@ Line 3: / Line 3: @@
 <StructureSection load='6kcz' size='340' side='right'caption='[[6kcz]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6kcz]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KCZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KCZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kcz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5z4i 5z4i]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KCZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KCZ 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>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">USP20, KIAA1003, LSFR3A, VDU2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6kcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kcz OCA], [http://pdbe.org/6kcz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kcz RCSB], [http://www.ebi.ac.uk/pdbsum/6kcz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kcz ProSAT]</span></td></tr>
@@ Line 10: / Line 11: @@
 == Function ==
 [[http://www.uniprot.org/uniprot/UBP20_HUMAN UBP20_HUMAN]] Deubiquitinating enzyme involved in beta-2 adrenergic receptor (ADRB2) recycling. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.<ref>PMID:12056827</ref> <ref>PMID:12865408</ref> <ref>PMID:15776016</ref> <ref>PMID:19424180</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Deubiquitinase USP20/VDU2 has been demonstrated to play important roles in multiple cellular processes by controlling the life span of substrate proteins including hypoxia-inducible factor HIF1alpha, and so forth. USP20 contains four distinct structural domains including the N-terminal zinc-finger ubiquitin binding domain (ZnF-UBP), the catalytic domain (USP domain), and two tandem DUSP domains, and none of the structures for these four domains has been solved. Meanwhile, except for the ZnF-UBP domain, the biological functions for USP20's catalytic domain and tandem DUSP domains have been at least partially clarified. Here in this study, we determined the solution structure of USP20 ZnF-UBP domain and investigated its binding properties with mono-ubiquitin and poly-ubiquitin (K48-linked di-ubiquitin) by using NMR and molecular modeling techniques. USP20's ZnF-UBP domain forms a spherically shaped fold consisting of a central beta-sheet with either one alpha-helix or two alpha-helices packed on each side of the sheet. However, although having formed a canonical core structure essential for ubiquitin recognition, USP20 ZnF-UBP presents weak ubiquitin binding capacity. The structural basis for understanding USP20 ZnF-UBP's ubiquitin binding capacity was revealed by NMR data-driven docking. Although the electrostatic interactions between D264 of USP5 (E87 in USP20 ZnF-UBP) and R74 of ubiquitin are kept, the loss of the extensive interactions formed between ubiquitin's di-glycine motif and the conserved and non-conserved residues of USP20 ZnF-UBP domain (W41, E55, and Y84) causes a significant decrease in its binding affinity to ubiquitin. Our findings indicate that USP20 ZnF-UBP domain might have a physiological role unrelated to its ubiquitin binding capacity.
+Structural and functional studies of USP20 ZnF-UBP domain by NMR.,Yang Y, Ding Y, Zhou C, Wen Y, Zhang N Protein Sci. 2019 Sep;28(9):1606-1619. doi: 10.1002/pro.3675. Epub 2019 Aug 9. PMID:31278784<ref>PMID:31278784</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6kcz" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Ubiquitinyl hydrolase 1]]

6kcz

From Proteopedia

Revision as of 05:44, 21 August 2019

Solution structure of the ZnF-UBP domain of USP20/VDU2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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