6z7v

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Mindy2 (C266A) in complex with Lys48 linked di-ubiquitin (K48-Ub2)

Structural highlights

6z7v is a 9 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 2.65Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MINY2_HUMAN Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins (PubMed:27292798). Binds to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33', 'Lys-48' and 'Lys-63' (PubMed:28082312). May play a regulatory role at the level of protein turnover (PubMed:27292798).^[1] ^[2]

Publication Abstract from PubMed

Of the eight distinct polyubiquitin (polyUb) linkages that can be assembled, the roles of K48-linked polyUb (K48-polyUb) are the most established, with K48-polyUb modified proteins being targeted for degradation. MINDY1 and MINDY2 are members of the MINDY family of deubiquitinases (DUBs) that have exquisite specificity for cleaving K48-polyUb, yet we have a poor understanding of their catalytic mechanism. Here, we analyze the crystal structures of MINDY1 and MINDY2 alone and in complex with monoUb, di-, and penta-K48-polyUb, identifying 5 distinct Ub binding sites in the catalytic domain that explain how these DUBs sense both Ub chain length and linkage type to cleave K48-polyUb chains. The activity of MINDY1/2 is inhibited by the Cys-loop, and we find that substrate interaction relieves autoinhibition to activate these DUBs. We also find that MINDY1/2 use a non-canonical catalytic triad composed of Cys-His-Thr. Our findings highlight multiple layers of regulation modulating DUB activity in MINDY1 and MINDY2.

Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2.,Abdul Rehman SA, Armstrong LA, Lange SM, Kristariyanto YA, Grawert TW, Knebel A, Svergun DI, Kulathu Y Mol Cell. 2021 Sep 10. pii: S1097-2765(21)00691-2. doi:, 10.1016/j.molcel.2021.08.024. PMID:34529927^[3]

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

References

↑ Abdul Rehman SA, Kristariyanto YA, Choi SY, Nkosi PJ, Weidlich S, Labib K, Hofmann K, Kulathu Y. MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes. Mol Cell. 2016 Jul 7;63(1):146-55. doi: 10.1016/j.molcel.2016.05.009. Epub 2016, Jun 9. PMID:27292798 doi:http://dx.doi.org/10.1016/j.molcel.2016.05.009
↑ Kristariyanto YA, Abdul Rehman SA, Weidlich S, Knebel A, Kulathu Y. A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains. EMBO Rep. 2017 Jan 12. pii: e201643205. doi: 10.15252/embr.201643205. PMID:28082312 doi:http://dx.doi.org/10.15252/embr.201643205
↑ Abdul Rehman SA, Armstrong LA, Lange SM, Kristariyanto YA, Grawert TW, Knebel A, Svergun DI, Kulathu Y. Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2. Mol Cell. 2021 Sep 10. pii: S1097-2765(21)00691-2. doi:, 10.1016/j.molcel.2021.08.024. PMID:34529927 doi:http://dx.doi.org/10.1016/j.molcel.2021.08.024

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/6z7v"

Categories: Homo sapiens | Large Structures | Abdul Rehman SA | Kulathu Y | Lange SM

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6z7v is ON HOLD
+==Crystal structure of Mindy2 (C266A) in complex with Lys48 linked di-ubiquitin (K48-Ub2)==
+<StructureSection load='6z7v' size='340' side='right'caption='[[6z7v]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6z7v]] is a 9 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=6Z7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z7V 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]] 2.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=6z7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z7v OCA], [https://pdbe.org/6z7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z7v RCSB], [https://www.ebi.ac.uk/pdbsum/6z7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z7v ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MINY2_HUMAN MINY2_HUMAN] Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins (PubMed:27292798). Binds to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33', 'Lys-48' and 'Lys-63' (PubMed:28082312). May play a regulatory role at the level of protein turnover (PubMed:27292798).<ref>PMID:27292798</ref> <ref>PMID:28082312</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Of the eight distinct polyubiquitin (polyUb) linkages that can be assembled, the roles of K48-linked polyUb (K48-polyUb) are the most established, with K48-polyUb modified proteins being targeted for degradation. MINDY1 and MINDY2 are members of the MINDY family of deubiquitinases (DUBs) that have exquisite specificity for cleaving K48-polyUb, yet we have a poor understanding of their catalytic mechanism. Here, we analyze the crystal structures of MINDY1 and MINDY2 alone and in complex with monoUb, di-, and penta-K48-polyUb, identifying 5 distinct Ub binding sites in the catalytic domain that explain how these DUBs sense both Ub chain length and linkage type to cleave K48-polyUb chains. The activity of MINDY1/2 is inhibited by the Cys-loop, and we find that substrate interaction relieves autoinhibition to activate these DUBs. We also find that MINDY1/2 use a non-canonical catalytic triad composed of Cys-His-Thr. Our findings highlight multiple layers of regulation modulating DUB activity in MINDY1 and MINDY2.
-Authors: Abdul Rehman, S.A., Lange, S.M., Kulathu, Y.
+Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2.,Abdul Rehman SA, Armstrong LA, Lange SM, Kristariyanto YA, Grawert TW, Knebel A, Svergun DI, Kulathu Y Mol Cell. 2021 Sep 10. pii: S1097-2765(21)00691-2. doi:, 10.1016/j.molcel.2021.08.024. PMID:34529927<ref>PMID:34529927</ref>
-Description: Crystal structure of Mindy2 (C266A) in complex with Lys48 linked di-ubiquitin (K48-Ub2)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Lange, S.M]]
+<div class="pdbe-citations 6z7v" style="background-color:#fffaf0;"></div>
-[[Category: Abdul Rehman, S.A]]
+== References ==
-[[Category: Kulathu, Y]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Abdul Rehman SA]]
+[[Category: Kulathu Y]]
+[[Category: Lange SM]]

6z7v

From Proteopedia

Current revision

Crystal structure of Mindy2 (C266A) in complex with Lys48 linked di-ubiquitin (K48-Ub2)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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