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5z2c

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==Crystal structure of ALPK-1 N-terminal domain in complex with ADP-heptose==
==Crystal structure of ALPK-1 N-terminal domain in complex with ADP-heptose==
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<StructureSection load='5z2c' size='340' side='right' caption='[[5z2c]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
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<StructureSection load='5z2c' size='340' side='right'caption='[[5z2c]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5z2c]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z2C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z2C FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5z2c]] is a 9 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=5Z2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z2C FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AYU:[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2S,3S,4S,5S,6R)-6-[(1S)-1,2-bis(oxidanyl)ethyl]-3,4,5-tris(oxidanyl)oxan-2-yl]+hydrogen+phosphate'>AYU</scene></td></tr>
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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]] 2.594&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALPK1, KIAA1527, LAK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=AYU:[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2S,3S,4S,5S,6R)-6-[(1S)-1,2-bis(oxidanyl)ethyl]-3,4,5-tris(oxidanyl)oxan-2-yl]+hydrogen+phosphate'>AYU</scene></td></tr>
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<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=5z2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z2c OCA], [http://pdbe.org/5z2c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z2c RCSB], [http://www.ebi.ac.uk/pdbsum/5z2c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z2c ProSAT]</span></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=5z2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z2c OCA], [https://pdbe.org/5z2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z2c RCSB], [https://www.ebi.ac.uk/pdbsum/5z2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z2c ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/ALPK1_HUMAN ALPK1_HUMAN]] Kinase that recognizes phosphorylation sites in which the surrounding peptides have an alpha-helical conformation.
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[https://www.uniprot.org/uniprot/ALPK1_HUMAN ALPK1_HUMAN] Kinase that recognizes phosphorylation sites in which the surrounding peptides have an alpha-helical conformation.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Immune recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors often activates proinflammatory NF-kappaB signalling(1). Recent studies indicate that the bacterial metabolite D-glycero-beta-D-manno-heptose 1,7-bisphosphate (HBP) can activate NF-kappaB signalling in host cytosol(2-4), but it is unclear whether HBP is a genuine PAMP and the cognate pattern recognition receptor has not been identified. Here we combined a transposon screen in Yersinia pseudotuberculosis with biochemical analyses and identified ADP-beta-D-manno-heptose (ADP-Hep), which mediates type III secretion system-dependent NF-kappaB activation and cytokine expression. ADP-Hep, but not other heptose metabolites, could enter host cytosol to activate NF-kappaB. A CRISPR-Cas9 screen showed that activation of NF-kappaB by ADP-Hep involves an ALPK1 (alpha-kinase 1)-TIFA (TRAF-interacting protein with forkhead-associated domain) axis. ADP-Hep directly binds the N-terminal domain of ALPK1, stimulating its kinase domain to phosphorylate and activate TIFA. The crystal structure of the N-terminal domain of ALPK1 and ADP-Hep in complex revealed the atomic mechanism of this ligand-receptor recognition process. HBP was transformed by host adenylyltransferases into ADP-heptose 7-P, which could activate ALPK1 to a lesser extent than ADP-Hep. ADP-Hep (but not HBP) alone or during bacterial infection induced Alpk1-dependent inflammation in mice. Our findings identify ALPK1 and ADP-Hep as a pattern recognition receptor and an effective immunomodulator, respectively.
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Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose.,Zhou P, She Y, Dong N, Li P, He H, Borio A, Wu Q, Lu S, Ding X, Cao Y, Xu Y, Gao W, Dong M, Ding J, Wang DC, Zamyatina A, Shao F Nature. 2018 Aug 15. pii: 10.1038/s41586-018-0433-3. doi:, 10.1038/s41586-018-0433-3. PMID:30111836<ref>PMID:30111836</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5z2c" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Ding, J]]
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[[Category: Large Structures]]
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[[Category: Shao, F]]
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[[Category: Ding J]]
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[[Category: She, Y]]
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[[Category: Shao F]]
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[[Category: Immune system]]
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[[Category: She Y]]
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[[Category: Kinase]]
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[[Category: Pattern recognition receptor]]
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Current revision

Crystal structure of ALPK-1 N-terminal domain in complex with ADP-heptose

PDB ID 5z2c

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