7qqk
From Proteopedia
(Difference between revisions)
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<StructureSection load='7qqk' size='340' side='right'caption='[[7qqk]], [[Resolution|resolution]] 3.80Å' scene=''> | <StructureSection load='7qqk' size='340' side='right'caption='[[7qqk]], [[Resolution|resolution]] 3.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[7qqk]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[7qqk]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Microbacterium_terrae Microbacterium terrae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QQK FirstGlance]. <br> |
| - | </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=7qqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qqk OCA], [https://pdbe.org/7qqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qqk RCSB], [https://www.ebi.ac.uk/pdbsum/7qqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qqk ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8Å</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=7qqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qqk OCA], [https://pdbe.org/7qqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qqk RCSB], [https://www.ebi.ac.uk/pdbsum/7qqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qqk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/A0A0M2HE71_9MICO A0A0M2HE71_9MICO] | |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Cyclic nucleotide signalling is a key component of antiviral defence in all domains of life. Viral detection activates a nucleotide cyclase to generate a second messenger, resulting in activation of effector proteins. This is exemplified by the metazoan cGAS-STING innate immunity pathway(1), which originated in bacteria(2). These defence systems require a sensor domain to bind the cyclic nucleotide and are often coupled with an effector domain that, when activated, causes cell death by destroying essential biomolecules(3). One example is the Toll/interleukin-1 receptor (TIR) domain, which degrades the essential cofactor NAD(+) when activated in response to infection in plants and bacteria(2,4,5) or during programmed nerve cell death(6). Here we show that a bacterial antiviral defence system generates a cyclic tri-adenylate that binds to a TIR-SAVED effector, acting as the 'glue' to allow assembly of an extended superhelical solenoid structure. Adjacent TIR subunits interact to organize and complete a composite active site, allowing NAD(+) degradation. Activation requires extended filament formation, both in vitro and in vivo. Our study highlights an example of large-scale molecular assembly controlled by cyclic nucleotides and reveals key details of the mechanism of TIR enzyme activation. | Cyclic nucleotide signalling is a key component of antiviral defence in all domains of life. Viral detection activates a nucleotide cyclase to generate a second messenger, resulting in activation of effector proteins. This is exemplified by the metazoan cGAS-STING innate immunity pathway(1), which originated in bacteria(2). These defence systems require a sensor domain to bind the cyclic nucleotide and are often coupled with an effector domain that, when activated, causes cell death by destroying essential biomolecules(3). One example is the Toll/interleukin-1 receptor (TIR) domain, which degrades the essential cofactor NAD(+) when activated in response to infection in plants and bacteria(2,4,5) or during programmed nerve cell death(6). Here we show that a bacterial antiviral defence system generates a cyclic tri-adenylate that binds to a TIR-SAVED effector, acting as the 'glue' to allow assembly of an extended superhelical solenoid structure. Adjacent TIR subunits interact to organize and complete a composite active site, allowing NAD(+) degradation. Activation requires extended filament formation, both in vitro and in vivo. Our study highlights an example of large-scale molecular assembly controlled by cyclic nucleotides and reveals key details of the mechanism of TIR enzyme activation. | ||
| - | Cyclic nucleotide-induced helical structure activates a TIR immune effector.,Hogrel G, Guild A, Graham S, Rickman H, Gruschow S, Bertrand Q, Spagnolo L, White MF Nature. 2022 Aug;608(7924):808-812. doi: 10.1038/s41586-022-05070-9. Epub 2022, Aug 10. PMID:35948638<ref>PMID:35948638</ref> | + | Cyclic nucleotide-induced helical structure activates a TIR immune effector.,Hogrel G, Guild A, Graham S, Rickman H, Gruschow S, Bertrand Q, Spagnolo L, White MF Nature. 2022 Aug;608(7924):808-812. doi: 10.1038/s41586-022-05070-9. Epub 2022 , Aug 10. PMID:35948638<ref>PMID:35948638</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Microbacterium | + | [[Category: Microbacterium terrae]] |
[[Category: Guild A]] | [[Category: Guild A]] | ||
[[Category: Hogrel G]] | [[Category: Hogrel G]] | ||
[[Category: Spagnolo L]] | [[Category: Spagnolo L]] | ||
[[Category: White MF]] | [[Category: White MF]] | ||
Current revision
TIR-SAVED effector bound to cA3
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