5ysj

From Proteopedia

(Difference between revisions)

Revision as of 07:20, 29 August 2018

SdeA mART-C domain WT apo

Structural highlights

5ysj is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SDEA_LEGPH] Secreted effector that interferes with the host cell ubiquitin pathway and is required for intracellular bacterial replication. Catalyzes the ubiquitination of several mammalian Rab proteins (Rab33b, Rab1, Rab6a and Rab30) during L.pneumophila infection, without engaging the standard cellular enzyme cascade (E1 and E2). Transfers an ADP-ribose moiety from NAD to the 'Arg-42' residue of ubiquitin in a reaction that releases nicotinamide. The modified ubiquitin is subsequently transferred to the substrate protein through an unknown mechanism that results in the release of AMP. Cannot ubiquitinate the endosomal Rab5 or the cytoskeletal small GTPase Rac1 (PubMed:27049943). Also acts as a deubiquitinase (DUB), catalyzing the cleavage of three of the most abundant polyubiquitin chains ('Lys-11', 'Lys-48' and 'Lys-63') with a distinct preference for 'Lys-63' linkages; is thus able to efficiently remove 'Lys-63'-linked polyubiquitin chains from the phagosomal surface. Is also able to remove NEDD8 from neddylated proteins, but is unable to recognize SUMO. The DUB activity of SdeA is important for regulating the dynamics of ubiquitin association with the bacterial phagosome, but is dispensable for its role in intracellular bacterial replication (PubMed:26598703).^[1] ^[2]

Publication Abstract from PubMed

Conventional ubiquitylation occurs through an ATP-dependent three-enzyme cascade (E1, E2, and E3) that mediates the covalent conjugation of the C-terminus of ubiquitin to a lysine on the substrate. SdeA, which belongs to the SidE effector family of Legionella pneumophila, can transfer ubiquitin to endoplasmic reticulum-associated Rab-family GTPases in a manner independent of E1 and E2 enzymes. The novel ubiquitin-modifying enzyme SdeA utilizes NAD(+) as a cofactor to attach ubiquitin to a serine residue of the substrate. Here, to elucidate the coupled enzymatic reaction of NAD+ hydrolysis and ADP-ribosylation of ubiquitin in SdeA, we characterized the mono-ADP-ribosyltransferase domain of SdeA and show that it consists of two sub-domains termed mART-N and mART-C. The crystal structure of the mART-C domain of SdeA was also determined in free form and in complex with NAD(+) at high resolution. Furthermore, the spatial orientations of the N-terminal deubiquitylase, phosphodiesterase, mono-ADP-ribosyltransferase, and C-terminal coiled-coil domains within the 180-kDa full-length SdeA were determined. These results provide insight into the unusual ubiquitylation mechanism of SdeA and expand our knowledge on the structure-function of mono-ADP-ribosyltransferases.

Structural and Biochemical Study of the Mono-ADP-Ribosyltransferase Domain of SdeA, a Ubiquitylating/Deubiquitylating Enzyme from Legionella pneumophila.,Kim L, Kwon DH, Kim BH, Kim J, Park MR, Park ZY, Song HK J Mol Biol. 2018 Aug 17;430(17):2843-2856. doi: 10.1016/j.jmb.2018.05.043. Epub, 2018 Jun 2. PMID:29870726^[3]

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

References

↑ Sheedlo MJ, Qiu J, Tan Y, Paul LN, Luo ZQ, Das C. Structural basis of substrate recognition by a bacterial deubiquitinase important for dynamics of phagosome ubiquitination. Proc Natl Acad Sci U S A. 2015 Nov 23. pii: 201514568. PMID:26598703 doi:http://dx.doi.org/10.1073/pnas.1514568112
↑ Qiu J, Sheedlo MJ, Yu K, Tan Y, Nakayasu ES, Das C, Liu X, Luo ZQ. Ubiquitination independent of E1 and E2 enzymes by bacterial effectors. Nature. 2016 May 5;533(7601):120-4. doi: 10.1038/nature17657. Epub 2016 Apr 6. PMID:27049943 doi:http://dx.doi.org/10.1038/nature17657
↑ Kim L, Kwon DH, Kim BH, Kim J, Park MR, Park ZY, Song HK. Structural and Biochemical Study of the Mono-ADP-Ribosyltransferase Domain of SdeA, a Ubiquitylating/Deubiquitylating Enzyme from Legionella pneumophila. J Mol Biol. 2018 Aug 17;430(17):2843-2856. doi: 10.1016/j.jmb.2018.05.043. Epub, 2018 Jun 2. PMID:29870726 doi:http://dx.doi.org/10.1016/j.jmb.2018.05.043

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/5ysj"

Categories: Kim, L | Kwon, D H | Song, H K | E3 ligase | Hydrolase

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5ysj is ON HOLD  until Paper Publication
+==SdeA mART-C domain WT apo==
+<StructureSection load='5ysj' size='340' side='right' caption='[[5ysj]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5ysj]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YSJ FirstGlance]. <br>
+</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=5ysj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ysj OCA], [http://pdbe.org/5ysj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ysj RCSB], [http://www.ebi.ac.uk/pdbsum/5ysj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ysj ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/SDEA_LEGPH SDEA_LEGPH]] Secreted effector that interferes with the host cell ubiquitin pathway and is required for intracellular bacterial replication. Catalyzes the ubiquitination of several mammalian Rab proteins (Rab33b, Rab1, Rab6a and Rab30) during L.pneumophila infection, without engaging the standard cellular enzyme cascade (E1 and E2). Transfers an ADP-ribose moiety from NAD to the 'Arg-42' residue of ubiquitin in a reaction that releases nicotinamide. The modified ubiquitin is subsequently transferred to the substrate protein through an unknown mechanism that results in the release of AMP. Cannot ubiquitinate the endosomal Rab5 or the cytoskeletal small GTPase Rac1 (PubMed:27049943). Also acts as a deubiquitinase (DUB), catalyzing the cleavage of three of the most abundant polyubiquitin chains ('Lys-11', 'Lys-48' and 'Lys-63') with a distinct preference for 'Lys-63' linkages; is thus able to efficiently remove 'Lys-63'-linked polyubiquitin chains from the phagosomal surface. Is also able to remove NEDD8 from neddylated proteins, but is unable to recognize SUMO. The DUB activity of SdeA is important for regulating the dynamics of ubiquitin association with the bacterial phagosome, but is dispensable for its role in intracellular bacterial replication (PubMed:26598703).<ref>PMID:26598703</ref> <ref>PMID:27049943</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Conventional ubiquitylation occurs through an ATP-dependent three-enzyme cascade (E1, E2, and E3) that mediates the covalent conjugation of the C-terminus of ubiquitin to a lysine on the substrate. SdeA, which belongs to the SidE effector family of Legionella pneumophila, can transfer ubiquitin to endoplasmic reticulum-associated Rab-family GTPases in a manner independent of E1 and E2 enzymes. The novel ubiquitin-modifying enzyme SdeA utilizes NAD(+) as a cofactor to attach ubiquitin to a serine residue of the substrate. Here, to elucidate the coupled enzymatic reaction of NAD+ hydrolysis and ADP-ribosylation of ubiquitin in SdeA, we characterized the mono-ADP-ribosyltransferase domain of SdeA and show that it consists of two sub-domains termed mART-N and mART-C. The crystal structure of the mART-C domain of SdeA was also determined in free form and in complex with NAD(+) at high resolution. Furthermore, the spatial orientations of the N-terminal deubiquitylase, phosphodiesterase, mono-ADP-ribosyltransferase, and C-terminal coiled-coil domains within the 180-kDa full-length SdeA were determined. These results provide insight into the unusual ubiquitylation mechanism of SdeA and expand our knowledge on the structure-function of mono-ADP-ribosyltransferases.
-Authors:
+Structural and Biochemical Study of the Mono-ADP-Ribosyltransferase Domain of SdeA, a Ubiquitylating/Deubiquitylating Enzyme from Legionella pneumophila.,Kim L, Kwon DH, Kim BH, Kim J, Park MR, Park ZY, Song HK J Mol Biol. 2018 Aug 17;430(17):2843-2856. doi: 10.1016/j.jmb.2018.05.043. Epub, 2018 Jun 2. PMID:29870726<ref>PMID:29870726</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5ysj" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Kim, L]]
+[[Category: Kwon, D H]]
+[[Category: Song, H K]]
+[[Category: E3 ligase]]
+[[Category: Hydrolase]]

5ysj

From Proteopedia

Revision as of 07:20, 29 August 2018

SdeA mART-C domain WT apo

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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