6ei1

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the covalent complex between deubiquitinase ZUFSP (ZUP1) and Ubiquitin-PA

Structural highlights

6ei1 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 1.732Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ZUP1_HUMAN Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains. Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains (PubMed:29476094, PubMed:29563501, PubMed:29576528). Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage (PubMed:29576527, PubMed:29576528). Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress (PubMed:29563501).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Deubiquitinating enzymes (DUBs) regulate ubiquitin signaling by trimming ubiquitin chains or removing ubiquitin from modified substrates. Similar activities exist for ubiquitin-related modifiers, although the enzymes involved are usually not related. Here, we report human ZUFSP (also known as ZUP1 and C6orf113) and fission yeast Mug105 as founding members of a DUB family different from the six known DUB classes. The crystal structure of human ZUFSP in covalent complex with propargylated ubiquitin shows that the DUB family shares a fold with UFM1- and Atg8-specific proteases, but uses a different active site more similar to canonical DUB enzymes. ZUFSP family members differ widely in linkage specificity through differential use of modular ubiquitin-binding domains (UBDs). While the minimalistic Mug105 prefers K48 chains, ZUFSP uses multiple UBDs for its K63-specific endo-DUB activity. K63 specificity, localization, and protein interaction network suggest a role for ZUFSP in DNA damage response.

A family of unconventional deubiquitinases with modular chain specificity determinants.,Hermanns T, Pichlo C, Woiwode I, Klopffleisch K, Witting KF, Ovaa H, Baumann U, Hofmann K Nat Commun. 2018 Feb 23;9(1):799. doi: 10.1038/s41467-018-03148-5. PMID:29476094^[5]

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

References

↑ Hermanns T, Pichlo C, Woiwode I, Klopffleisch K, Witting KF, Ovaa H, Baumann U, Hofmann K. A family of unconventional deubiquitinases with modular chain specificity determinants. Nat Commun. 2018 Feb 23;9(1):799. doi: 10.1038/s41467-018-03148-5. PMID:29476094 doi:http://dx.doi.org/10.1038/s41467-018-03148-5
↑ Hewings DS, Heideker J, Ma TP, AhYoung AP, El Oualid F, Amore A, Costakes GT, Kirchhofer D, Brasher B, Pillow T, Popovych N, Maurer T, Schwerdtfeger C, Forrest WF, Yu K, Flygare J, Bogyo M, Wertz IE. Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes. Nat Commun. 2018 Mar 21;9(1):1162. PMID:29563501 doi:10.1038/s41467-018-03511-6
↑ Kwasna D, Abdul Rehman SA, Natarajan J, Matthews S, Madden R, De Cesare V, Weidlich S, Virdee S, Ahel I, Gibbs-Seymour I, Kulathu Y. Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability. Mol Cell. 2018 Mar 21. pii: S1097-2765(18)30142-4. doi:, 10.1016/j.molcel.2018.02.023. PMID:29576527 doi:http://dx.doi.org/10.1016/j.molcel.2018.02.023
↑ Haahr P, Borgermann N, Guo X, Typas D, Achuthankutty D, Hoffmann S, Shearer R, Sixma TK, Mailand N. ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome Stability. Mol Cell. 2018 Apr 5;70(1):165-174.e6. PMID:29576528 doi:10.1016/j.molcel.2018.02.024
↑ Hermanns T, Pichlo C, Woiwode I, Klopffleisch K, Witting KF, Ovaa H, Baumann U, Hofmann K. A family of unconventional deubiquitinases with modular chain specificity determinants. Nat Commun. 2018 Feb 23;9(1):799. doi: 10.1038/s41467-018-03148-5. PMID:29476094 doi:http://dx.doi.org/10.1038/s41467-018-03148-5

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/6ei1"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6ei1 is ON HOLD
+==Crystal structure of the covalent complex between deubiquitinase ZUFSP (ZUP1) and Ubiquitin-PA==
+<StructureSection load='6ei1' size='340' side='right'caption='[[6ei1]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ei1]] 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=6EI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EI1 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.732&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></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=6ei1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ei1 OCA], [https://pdbe.org/6ei1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ei1 RCSB], [https://www.ebi.ac.uk/pdbsum/6ei1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ei1 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ZUP1_HUMAN ZUP1_HUMAN] Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains. Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains (PubMed:29476094, PubMed:29563501, PubMed:29576528). Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage (PubMed:29576527, PubMed:29576528). Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress (PubMed:29563501).<ref>PMID:29476094</ref> <ref>PMID:29563501</ref> <ref>PMID:29576527</ref> <ref>PMID:29576528</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Deubiquitinating enzymes (DUBs) regulate ubiquitin signaling by trimming ubiquitin chains or removing ubiquitin from modified substrates. Similar activities exist for ubiquitin-related modifiers, although the enzymes involved are usually not related. Here, we report human ZUFSP (also known as ZUP1 and C6orf113) and fission yeast Mug105 as founding members of a DUB family different from the six known DUB classes. The crystal structure of human ZUFSP in covalent complex with propargylated ubiquitin shows that the DUB family shares a fold with UFM1- and Atg8-specific proteases, but uses a different active site more similar to canonical DUB enzymes. ZUFSP family members differ widely in linkage specificity through differential use of modular ubiquitin-binding domains (UBDs). While the minimalistic Mug105 prefers K48 chains, ZUFSP uses multiple UBDs for its K63-specific endo-DUB activity. K63 specificity, localization, and protein interaction network suggest a role for ZUFSP in DNA damage response.
-Authors: Pichlo, C., Baumann, U., Hofmann, K., Hermanns, T.
+A family of unconventional deubiquitinases with modular chain specificity determinants.,Hermanns T, Pichlo C, Woiwode I, Klopffleisch K, Witting KF, Ovaa H, Baumann U, Hofmann K Nat Commun. 2018 Feb 23;9(1):799. doi: 10.1038/s41467-018-03148-5. PMID:29476094<ref>PMID:29476094</ref>
-Description: Crystal structure of the covalent complex between deubiquitinase ZUFSP and Ubiquitin-PA
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Baumann, U]]
+<div class="pdbe-citations 6ei1" style="background-color:#fffaf0;"></div>
-[[Category: Pichlo, C]]
-[[Category: Hofmann, K]]
+==See Also==
-[[Category: Hermanns, T]]
+*[[3D structures of ubiquitin|3D structures of ubiquitin]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Baumann U]]
+[[Category: Hermanns T]]
+[[Category: Hofmann K]]
+[[Category: Pichlo C]]

6ei1

From Proteopedia

Current revision

Crystal structure of the covalent complex between deubiquitinase ZUFSP (ZUP1) and Ubiquitin-PA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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