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4hcn

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{{STRUCTURE_4hcn| PDB=4hcn | SCENE= }}
 
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===Crystal structure of Burkholderia pseudomallei effector protein CHBP in complex with ubiquitin===
 
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{{ABSTRACT_PUBMED_23175788}}
 
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==Function==
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==Crystal structure of Burkholderia pseudomallei effector protein CHBP in complex with ubiquitin==
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[[http://www.uniprot.org/uniprot/UBI4P_YEAST UBI4P_YEAST]] 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, and DNA-damage responses. 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 (By similarity).
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<StructureSection load='4hcn' size='340' side='right'caption='[[4hcn]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4hcn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei_K96243 Burkholderia pseudomallei K96243] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HCN FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hcn OCA], [https://pdbe.org/4hcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hcn RCSB], [https://www.ebi.ac.uk/pdbsum/4hcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hcn ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CIF_BURPS CIF_BURPS] Protein-glutamine deamidase effector that inhibits the host cell cycle and other key cellular processes such as the actin network and programmed-cell death (PubMed:19308257, PubMed:20688984, PubMed:19225106). Acts by mediating the side chain deamidation of 'Gln-40' of host NEDD8, converting it to glutamate, thereby abolishing the activity of cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (PubMed:20688984, PubMed:21903097). Inactivation of CRL complexes prevents ubiquitination and subsequent degradation of the cyclin-dependent kinase inhibitors CDKN1A/p21 and CDKN1B/p27, leading to G1 and G2 cell cycle arrests in host cells (PubMed:19308257). Deamidation of 'Gln-40' of host NEDD8 also triggers macrophage-specific programmed cell death (PubMed:23175788). Also able to catalyze deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate in vivo (PubMed:20688984). Also regulates the host NF-kappa-B signaling via activation of MAPK/ERK cascade: activation of host MAPK/ERK cascade is independent of CRL complexes inhibition, suggesting that Cif has other host protein targets than NEDD8 (PubMed:28166272, PubMed:29848489).<ref>PMID:19225106</ref> <ref>PMID:19308257</ref> <ref>PMID:20688984</ref> <ref>PMID:21903097</ref> <ref>PMID:23175788</ref> <ref>PMID:28166272</ref> <ref>PMID:29848489</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Targeting eukaryotic proteins for deamidation modification is increasingly appreciated as a general bacterial virulence mechanism. Here, we present an atomic view of how a bacterial deamidase effector, cycle-inhibiting factor homolog in Burkholderia pseudomallei (CHBP), recognizes its host targets, ubiquitin (Ub) and Ub-like neural precursor cell expressed, developmentally down-regulated 8 (NEDD8), and catalyzes site-specific deamidation. Crystal structures of CHBP-Ub/NEDD8 complexes show that Ub and NEDD8 are similarly cradled by a large cleft in CHBP with four contacting surfaces. The pattern of Ub/NEDD8 recognition by CHBP resembles that by the E1 activation enzyme, which critically involves the Lys-11 surface in Ub/NEDD8. Close examination of the papain-like catalytic center reveals structural determinants of CHBP being an obligate glutamine deamidase. Molecular-dynamics simulation identifies Gln-31/Glu-31 of Ub/NEDD8 as one key determinant of CHBP substrate preference for NEDD8. Inspired by the idea of using the unique bacterial activity as a tool, we further discover that CHBP-catalyzed NEDD8 deamidation triggers macrophage-specific apoptosis, which predicts a previously unknown macrophage-specific proapoptotic signal that is negatively regulated by neddylation-mediated protein ubiquitination/degradation.
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==About this Structure==
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Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis.,Yao Q, Cui J, Wang J, Li T, Wan X, Luo T, Gong YN, Xu Y, Huang N, Shao F Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20395-400. doi:, 10.1073/pnas.1210831109. Epub 2012 Nov 21. PMID:23175788<ref>PMID:23175788</ref>
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[[4hcn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burps Burps] and [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HCN OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:023175788</ref><references group="xtra"/><references/>
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</div>
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[[Category: Baker's yeast]]
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<div class="pdbe-citations 4hcn" style="background-color:#fffaf0;"></div>
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[[Category: Burps]]
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== References ==
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[[Category: Cui, J.]]
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<references/>
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[[Category: Shao, F.]]
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__TOC__
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[[Category: Yao, Q.]]
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</StructureSection>
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[[Category: Zhu, Y.]]
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[[Category: Burkholderia pseudomallei K96243]]
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[[Category: Nedd8]]
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[[Category: Large Structures]]
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[[Category: Protein binding]]
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[[Category: Saccharomyces cerevisiae S288C]]
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[[Category: Ubiquitin]]
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[[Category: Cui J]]
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[[Category: Ubiquitin/nedd8 deamidase]]
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[[Category: Shao F]]
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[[Category: Yao Q]]
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[[Category: Zhu Y]]

Current revision

Crystal structure of Burkholderia pseudomallei effector protein CHBP in complex with ubiquitin

PDB ID 4hcn

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