6o1b

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Current revision (14:50, 13 March 2024) (edit) (undo)
 
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<StructureSection load='6o1b' size='340' side='right'caption='[[6o1b]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
<StructureSection load='6o1b' size='340' side='right'caption='[[6o1b]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6o1b]] is a 1 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=6O1B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O1B FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6o1b]] is a 1 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=6O1B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O1B 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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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]] 1.67&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SARM1, KIAA0524, SAMD2, SARM ([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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=6o1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o1b OCA], [http://pdbe.org/6o1b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o1b RCSB], [http://www.ebi.ac.uk/pdbsum/6o1b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o1b 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=6o1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o1b OCA], [https://pdbe.org/6o1b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o1b RCSB], [https://www.ebi.ac.uk/pdbsum/6o1b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o1b ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/SARM1_HUMAN SARM1_HUMAN]] Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38.<ref>PMID:15123841</ref> <ref>PMID:16964262</ref> <ref>PMID:16985498</ref> <ref>PMID:20306472</ref>
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[https://www.uniprot.org/uniprot/SARM1_HUMAN SARM1_HUMAN] Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38.<ref>PMID:15123841</ref> <ref>PMID:16964262</ref> <ref>PMID:16985498</ref> <ref>PMID:20306472</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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SARM1 (sterile alpha and TIR motif containing 1) is responsible for depletion of nicotinamide adenine dinucleotide in its oxidized form (NAD(+)) during Wallerian degeneration associated with neuropathies. Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors recognize pathogen effector proteins and trigger localized cell death to restrict pathogen infection. Both processes depend on closely related Toll/interleukin-1 receptor (TIR) domains in these proteins, which, as we show, feature self-association-dependent NAD(+) cleavage activity associated with cell death signaling. We further show that SARM1 SAM (sterile alpha motif) domains form an octamer essential for axon degeneration that contributes to TIR domain enzymatic activity. The crystal structures of ribose and NADP(+) (the oxidized form of nicotinamide adenine dinucleotide phosphate) complexes of SARM1 and plant NLR RUN1 TIR domains, respectively, reveal a conserved substrate binding site. NAD(+) cleavage by TIR domains is therefore a conserved feature of animal and plant cell death signaling pathways.
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NAD(+) cleavage activity by animal and plant TIR domains in cell death pathways.,Horsefield S, Burdett H, Zhang X, Manik MK, Shi Y, Chen J, Qi T, Gilley J, Lai JS, Rank MX, Casey LW, Gu W, Ericsson DJ, Foley G, Hughes RO, Bosanac T, von Itzstein M, Rathjen JP, Nanson JD, Boden M, Dry IB, Williams SJ, Staskawicz BJ, Coleman MP, Ve T, Dodds PN, Kobe B Science. 2019 Aug 23;365(6455):793-799. doi: 10.1126/science.aax1911. PMID:31439792<ref>PMID:31439792</ref>
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==See Also==
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*[[SARM1 3D structures|SARM1 3D structures]]
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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 6o1b" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Boden, M]]
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[[Category: Boden M]]
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[[Category: Bosanac, T]]
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[[Category: Bosanac T]]
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[[Category: Burdett, H]]
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[[Category: Burdett H]]
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[[Category: Casey, L]]
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[[Category: Casey L]]
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[[Category: Chen, J]]
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[[Category: Chen J]]
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[[Category: Coleman, M P]]
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[[Category: Coleman MP]]
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[[Category: Dodds, P N]]
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[[Category: Dodds PN]]
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[[Category: Dry, I B]]
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[[Category: Dry IB]]
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[[Category: Ericsson, D J]]
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[[Category: Ericsson DJ]]
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[[Category: Foley, G]]
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[[Category: Foley G]]
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[[Category: Gilley, J]]
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[[Category: Gilley J]]
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[[Category: Gu, W]]
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[[Category: Gu W]]
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[[Category: Horsefield, S]]
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[[Category: Horsefield S]]
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[[Category: Hughes, R O]]
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[[Category: Hughes RO]]
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[[Category: Itzstein, M von]]
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[[Category: Kobe B]]
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[[Category: Kobe, B]]
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[[Category: Lai J]]
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[[Category: Lai, J]]
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[[Category: Manik MK]]
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[[Category: Manik, M K]]
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[[Category: Nanson JD]]
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[[Category: Nanson, J D]]
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[[Category: Rank M]]
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[[Category: Rank, M]]
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[[Category: Rathjen JP]]
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[[Category: Rathjen, J P]]
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[[Category: Shi Y]]
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[[Category: Shi, Y]]
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[[Category: Staskawicz BJ]]
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[[Category: Staskawicz, B J]]
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[[Category: Tiancong Q]]
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[[Category: Tiancong, Q]]
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[[Category: Ve T]]
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[[Category: Ve, T]]
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[[Category: Williams SJ]]
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[[Category: Williams, S J]]
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[[Category: Zhang X]]
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[[Category: Zhang, X]]
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[[Category: Von Itzstein M]]
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[[Category: Axon degeneration]]
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[[Category: Signaling protein]]
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Current revision

Crystal structure of the TIR domain G601P mutant from human SARM1, crystal form 1

PDB ID 6o1b

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