6sak

From Proteopedia

(Difference between revisions)

Current revision

Structure of the OTULINcat C129A - SNX27 PDZ domain complex.

Structural highlights

6sak is a 4 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 2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

OTUL_HUMAN Deubiquitinase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response. Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates. Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex. Acts as a negative regulator of NF-kappa-B by counteracting activity of the LUBAC complex. Plays a key role in innate immune response: required to restrict linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

OTULIN (OTU Deubiquitinase With Linear Linkage Specificity) specifically hydrolyzes methionine1 (Met1)-linked ubiquitin chains conjugated by LUBAC (linear ubiquitin chain assembly complex). Here we report on the mass spectrometric identification of the OTULIN interactor SNX27 (sorting nexin 27), an adaptor of the endosomal retromer complex responsible for protein recycling to the cell surface. The C-terminal PDZ-binding motif (PDZbm) in OTULIN associates with the cargo-binding site in the PDZ domain of SNX27. By solving the structure of the OTU domain in complex with the PDZ domain, we demonstrate that a second interface contributes to the selective, high affinity interaction of OTULIN and SNX27. SNX27 does not affect OTULIN catalytic activity, OTULIN-LUBAC binding or Met1-linked ubiquitin chain homeostasis. However, via association, OTULIN antagonizes SNX27-dependent cargo loading, binding of SNX27 to the VPS26A-retromer subunit and endosome-to-plasma membrane trafficking. Thus, we define an additional, non-catalytic function of OTULIN in the regulation of SNX27-retromer assembly and recycling to the cell surface.

Regulation of the endosomal SNX27-retromer by OTULIN.,Stangl A, Elliott PR, Pinto-Fernandez A, Bonham S, Harrison L, Schaub A, Kutzner K, Keusekotten K, Pfluger PT, El Oualid F, Kessler BM, Komander D, Krappmann D Nat Commun. 2019 Sep 20;10(1):4320. doi: 10.1038/s41467-019-12309-z. PMID:31541095^[5]

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

References

↑ Mevissen TE, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SM, Ovaa H, Komander D. OTU Deubiquitinases Reveal Mechanisms of Linkage Specificity and Enable Ubiquitin Chain Restriction Analysis. Cell. 2013 Jul 3;154(1):169-84. doi: 10.1016/j.cell.2013.05.046. PMID:23827681 doi:10.1016/j.cell.2013.05.046
↑ Fiil BK, Damgaard RB, Wagner SA, Keusekotten K, Fritsch M, Bekker-Jensen S, Mailand N, Choudhary C, Komander D, Gyrd-Hansen M. OTULIN restricts Met1-linked ubiquitination to control innate immune signaling. Mol Cell. 2013 Jun 27;50(6):818-30. doi: 10.1016/j.molcel.2013.06.004. PMID:23806334 doi:http://dx.doi.org/10.1016/j.molcel.2013.06.004
↑ Keusekotten K, Elliott PR, Glockner L, Fiil BK, Damgaard RB, Kulathu Y, Wauer T, Hospenthal MK, Gyrd-Hansen M, Krappmann D, Hofmann K, Komander D. OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked Polyubiquitin. Cell. 2013 Jun 6;153(6):1312-26. doi: 10.1016/j.cell.2013.05.014. PMID:23746843 doi:10.1016/j.cell.2013.05.014
↑ Rivkin E, Almeida SM, Ceccarelli DF, Juang YC, MacLean TA, Srikumar T, Huang H, Dunham WH, Fukumura R, Xie G, Gondo Y, Raught B, Gingras AC, Sicheri F, Cordes SP. The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis. Nature. 2013 Jun 20;498(7454):318-24. doi: 10.1038/nature12296. Epub 2013 May 24. PMID:23708998 doi:10.1038/nature12296
↑ Stangl A, Elliott PR, Pinto-Fernandez A, Bonham S, Harrison L, Schaub A, Kutzner K, Keusekotten K, Pfluger PT, El Oualid F, Kessler BM, Komander D, Krappmann D. Regulation of the endosomal SNX27-retromer by OTULIN. Nat Commun. 2019 Sep 20;10(1):4320. doi: 10.1038/s41467-019-12309-z. PMID:31541095 doi:http://dx.doi.org/10.1038/s41467-019-12309-z

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/6sak"

Categories: Homo sapiens | Large Structures | Elliott PR | Komander D

@@ Line 3: / Line 3: @@
 <StructureSection load='6sak' size='340' side='right'caption='[[6sak]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6sak]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SAK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6sak]] is a 4 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=6SAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SAK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6sak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sak OCA], [http://pdbe.org/6sak PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sak RCSB], [http://www.ebi.ac.uk/pdbsum/6sak PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sak 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=6sak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sak OCA], [https://pdbe.org/6sak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sak RCSB], [https://www.ebi.ac.uk/pdbsum/6sak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sak ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/OTUL_HUMAN OTUL_HUMAN]] Deubiquitinase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response. Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates. Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex. Acts as a negative regulator of NF-kappa-B by counteracting activity of the LUBAC complex. Plays a key role in innate immune response: required to restrict linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling.<ref>PMID:23827681</ref> <ref>PMID:23806334</ref> <ref>PMID:23746843</ref> <ref>PMID:23708998</ref>  [[http://www.uniprot.org/uniprot/SNX27_HUMAN SNX27_HUMAN]] Involved in endocytic trafficking (By similarity). In T lymphocytes, participates in endocytic recycling pathway. Recruits PSCDBP and HT4R to early endosomes (By similarity).<ref>PMID:17351151</ref>
+[https://www.uniprot.org/uniprot/OTUL_HUMAN OTUL_HUMAN] Deubiquitinase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response. Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates. Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex. Acts as a negative regulator of NF-kappa-B by counteracting activity of the LUBAC complex. Plays a key role in innate immune response: required to restrict linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling.<ref>PMID:23827681</ref> <ref>PMID:23806334</ref> <ref>PMID:23746843</ref> <ref>PMID:23708998</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6sak" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Sorting nexin 3D structures|Sorting nexin 3D structures]]
+*[[Thioesterase 3D structures|Thioesterase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ubiquitinyl hydrolase 1]]
+[[Category: Elliott PR]]
-[[Category: Elliott, P R]]
+[[Category: Komander D]]
-[[Category: Komander, D]]
-[[Category: Hydrolase]]
-[[Category: Met1-specific deubiquitinase]]

6sak

From Proteopedia

Current revision

Structure of the OTULINcat C129A - SNX27 PDZ domain complex.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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