|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of SspH1 LRR domain in complex PKN1 HR1b domain== | | ==Crystal structure of SspH1 LRR domain in complex PKN1 HR1b domain== |
| - | <StructureSection load='4nkg' size='340' side='right' caption='[[4nkg]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4nkg' size='340' side='right'caption='[[4nkg]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nkg]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Salt1 Salt1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NKG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NKG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nkg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium_str._14028S Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NKG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nkh|4nkh]]</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=4nkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nkg OCA], [https://pdbe.org/4nkg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nkg RCSB], [https://www.ebi.ac.uk/pdbsum/4nkg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nkg ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">sspH1, STM14_1483 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=588858 SALT1]), PAK1, PKN, PKN1, PRK1, PRKCL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </span></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=4nkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nkg OCA], [http://pdbe.org/4nkg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nkg RCSB], [http://www.ebi.ac.uk/pdbsum/4nkg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nkg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SSPH1_SALT1 SSPH1_SALT1]] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway. Can ubiquitinate both ubiquitin and host PKN1. Down-modulates production of host proinflammatory cytokines by inhibiting NF-kappa-B-dependent gene expression, probably via interaction with PKN1.<ref>PMID:10564523</ref> <ref>PMID:12819095</ref> <ref>PMID:16611232</ref> <ref>PMID:18005683</ref> [[http://www.uniprot.org/uniprot/PKN1_HUMAN PKN1_HUMAN]] PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.<ref>PMID:8557118</ref> <ref>PMID:8621664</ref> <ref>PMID:9175763</ref> <ref>PMID:11104762</ref> <ref>PMID:12514133</ref> <ref>PMID:17332740</ref> <ref>PMID:18066052</ref> <ref>PMID:20188095</ref> <ref>PMID:21754995</ref> | + | [https://www.uniprot.org/uniprot/SSPH1_SALT1 SSPH1_SALT1] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway. Can ubiquitinate both ubiquitin and host PKN1. Down-modulates production of host proinflammatory cytokines by inhibiting NF-kappa-B-dependent gene expression, probably via interaction with PKN1.<ref>PMID:10564523</ref> <ref>PMID:12819095</ref> <ref>PMID:16611232</ref> <ref>PMID:18005683</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 20: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Protein kinase C]] | + | [[Category: Large Structures]] |
| - | [[Category: Salt1]] | + | [[Category: Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S]] |
| - | [[Category: Keszei, A F.A]] | + | [[Category: Keszei AFA]] |
| - | [[Category: Mccormick, C]] | + | [[Category: Mccormick C]] |
| - | [[Category: Rohde, J R]] | + | [[Category: Rohde JR]] |
| - | [[Category: Sicheri, F]] | + | [[Category: Sicheri F]] |
| - | [[Category: Tyers, M]] | + | [[Category: Tyers M]] |
| - | [[Category: Xiaojing, T]] | + | [[Category: Xiaojing T]] |
| - | [[Category: Zeqiraj, E]] | + | [[Category: Zeqiraj E]] |
| - | [[Category: Coiled-coil]]
| + | |
| - | [[Category: E3 ligase substrate interaction]]
| + | |
| - | [[Category: Leucine-rich repeat]]
| + | |
| - | [[Category: Ligase-transferase complex]]
| + | |
| Structural highlights
Function
SSPH1_SALT1 Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway. Can ubiquitinate both ubiquitin and host PKN1. Down-modulates production of host proinflammatory cytokines by inhibiting NF-kappa-B-dependent gene expression, probably via interaction with PKN1.[1] [2] [3] [4]
Publication Abstract from PubMed
IpaH proteins are bacterial-specific E3 enzymes that function as T3SS effectors in Salmonella, Shigella, and other gram-negative bacteria. IpaH enzymes recruit host substrates for ubiquitination via an LRR domain, which can inhibit the catalytic domain in the absence of substrate. The basis for substrate recognition and the alleviation of autoinhibition upon substrate binding is unknown. Here we report the X-ray structure of Salmonella SspH1 in complex with human PKN1. The LRR domain of SspH1 interacts specifically with the HR1b coiled-coil sub-domain of PKN1 in manner that sterically displaces the catalytic domain from the LRR domain, and thereby activates catalytic function. SspH1 catalyzes the ubiquitination and proteasome-dependent degradation of PKN1 in cells, which attenuates androgen receptor responsiveness but not NF-kappaB activity. These regulatory features are conserved in other IpaH-substrate interactions. Our results explain the mechanism whereby substrate recognition and enzyme autoregulation are coupled in this class of bacterial effector proteins.
Structure of an SspH1-PKN1 complex reveals the basis for host substrate recognition and mechanism of activation for a bacterial E3 ubiquitin ligase.,Keszei AF, Tang X, McCormick C, Zeqiraj E, Rohde JR, Tyers M, Sicheri F Mol Cell Biol. 2013 Nov 18. PMID:24248594[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Miao EA, Scherer CA, Tsolis RM, Kingsley RA, Adams LG, Baumler AJ, Miller SI. Salmonella typhimurium leucine-rich repeat proteins are targeted to the SPI1 and SPI2 type III secretion systems. Mol Microbiol. 1999 Nov;34(4):850-64. PMID:10564523
- ↑ Haraga A, Miller SI. A Salmonella enterica serovar typhimurium translocated leucine-rich repeat effector protein inhibits NF-kappa B-dependent gene expression. Infect Immun. 2003 Jul;71(7):4052-8. PMID:12819095
- ↑ Haraga A, Miller SI. A Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1. Cell Microbiol. 2006 May;8(5):837-46. PMID:16611232 doi:http://dx.doi.org/10.1111/j.1462-5822.2005.00670.x
- ↑ Rohde JR, Breitkreutz A, Chenal A, Sansonetti PJ, Parsot C. Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe. 2007 Mar 15;1(1):77-83. PMID:18005683 doi:10.1016/j.chom.2007.02.002
- ↑ Keszei AF, Tang X, McCormick C, Zeqiraj E, Rohde JR, Tyers M, Sicheri F. Structure of an SspH1-PKN1 complex reveals the basis for host substrate recognition and mechanism of activation for a bacterial E3 ubiquitin ligase. Mol Cell Biol. 2013 Nov 18. PMID:24248594 doi:http://dx.doi.org/10.1128/MCB.01360-13
|
