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| | <StructureSection load='6b7o' size='340' side='right'caption='[[6b7o]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='6b7o' size='340' side='right'caption='[[6b7o]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6b7o]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33152 Atcc 33152] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B7O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B7O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6b7o]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Legionella_pneumophila Legionella pneumophila]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B7O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</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]] 1.85Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpg2509 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 ATCC 33152]), UBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</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=6b7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b7o OCA], [http://pdbe.org/6b7o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b7o RCSB], [http://www.ebi.ac.uk/pdbsum/6b7o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b7o 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=6b7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b7o OCA], [https://pdbe.org/6b7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b7o RCSB], [https://www.ebi.ac.uk/pdbsum/6b7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b7o ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBC_HUMAN UBC_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> | + | [https://www.uniprot.org/uniprot/Q5ZSK8_LEGPH Q5ZSK8_LEGPH] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6b7o" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6b7o" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 33152]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Akturk, A]]
| + | [[Category: Legionella pneumophila]] |
| - | [[Category: Mao, Y]]
| + | [[Category: Akturk A]] |
| - | [[Category: Wasilko, J]]
| + | [[Category: Mao Y]] |
| - | [[Category: Adpr-ub]]
| + | [[Category: Wasilko J]] |
| - | [[Category: Cell invasion]]
| + | |
| - | [[Category: Legionella]] | + | |
| - | [[Category: Phosphodiesterase]] | + | |
| - | [[Category: Pr-ub]] | + | |
| - | [[Category: Sded]] | + | |
| - | [[Category: Ubiquitin]]
| + | |
| Structural highlights
Function
Q5ZSK8_LEGPH
Publication Abstract from PubMed
Ubiquitination is a post-translational modification that regulates many cellular processes in eukaryotes(1-4). The conventional ubiquitination cascade culminates in a covalent linkage between the C terminus of ubiquitin (Ub) and a target protein, usually on a lysine side chain(1,5). Recent studies of the Legionella pneumophila SidE family of effector proteins revealed a ubiquitination method in which a phosphoribosyl ubiquitin (PR-Ub) is conjugated to a serine residue on substrates via a phosphodiester bond(6-8). Here we present the crystal structure of a fragment of the SidE family member SdeA that retains ubiquitination activity, and determine the mechanism of this unique post-translational modification. The structure reveals that the catalytic module contains two distinct functional units: a phosphodiesterase domain and a mono-ADP-ribosyltransferase domain. Biochemical analysis shows that the mono-ADP-ribosyltransferase domain-mediated conversion of Ub to ADP-ribosylated Ub (ADPR-Ub) and the phosphodiesterase domain-mediated ligation of PR-Ub to substrates are two independent activities of SdeA. Furthermore, we present two crystal structures of a homologous phosphodiesterase domain from the SidE family member SdeD (9) in complexes with Ub and ADPR-Ub. The structures suggest a mechanism for how SdeA processes ADPR-Ub to PR-Ub and AMP, and conjugates PR-Ub to a serine residue in substrates. Our study establishes the molecular mechanism of phosphoribosyl-linked ubiquitination and will enable future studies of this unusual type of ubiquitination in eukaryotes.
Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector.,Akturk A, Wasilko DJ, Wu X, Liu Y, Zhang Y, Qiu J, Luo ZQ, Reiter KH, Brzovic PS, Klevit RE, Mao Y Nature. 2018 May;557(7707):729-733. doi: 10.1038/s41586-018-0147-6. Epub 2018 May, 23. PMID:29795346[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Akturk A, Wasilko DJ, Wu X, Liu Y, Zhang Y, Qiu J, Luo ZQ, Reiter KH, Brzovic PS, Klevit RE, Mao Y. Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector. Nature. 2018 May;557(7707):729-733. doi: 10.1038/s41586-018-0147-6. Epub 2018 May, 23. PMID:29795346 doi:http://dx.doi.org/10.1038/s41586-018-0147-6
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