9uga

From Proteopedia

(Difference between revisions)

Current revision

SARM1 senses DNA to promote NAD degradation

Structural highlights

9uga is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.06Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Detection of DNA is a fundamental strategy for life to recognize non-self or abnormal-self to subsequently trigger the downstream responses. However, the mechanism underlying DNA sensing is incompletely understood. Here, we show that a key neural executioner, sterile alpha and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1), senses double-stranded DNA (dsDNA) to promote cell death. dsDNA-bound and -activated SARM1 to degrade nicotinamide adenine dinucleotide (NAD(+)) in a sequence-independent manner. SARM1 bound dsDNA via the TIR domain, and lysine residues in the TIR domain contributed to dsDNA binding. In the cellular context, cytosolic dsDNA from dsDNA transfection or chemotherapy treatment was colocalized with SARM1 and activated SARM1 to elicit NAD(+) degradation and cell death, which was abrogated by SARM1 knockout or DNA-binding residue mutation. Consistently, SARM1 knockout blocked chemotherapy-induced neuropathy (CIN) in mice. Our results reveal SARM1 as a DNA sensor, which might be targetable for therapeutic interventions.

SARM1 senses dsDNA to promote NAD(+) degradation and cell death.,Wang L, Liu Q, Li S, Wang N, Chen Y, Chen J, Wang L, Huang Y, Sun Z, Dong L, Li S, Liu Q, Gao S, Ma X, Song C, Yang Q Cell. 2025 Oct 24:S0092-8674(25)01126-2. doi: 10.1016/j.cell.2025.09.026. PMID:41138726^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Liberati NT, Fitzgerald KA, Kim DH, Feinbaum R, Golenbock DT, Ausubel FM. Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6593-8. PMID:15123841 doi:http://dx.doi.org/10.1073/pnas.0308625101
↑ Carty M, Goodbody R, Schroder M, Stack J, Moynagh PN, Bowie AG. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat Immunol. 2006 Oct;7(10):1074-81. doi: 10.1038/ni1382. Epub 2006 Sep 10. PMID:16964262 doi:http://dx.doi.org/10.1038/ni1382
↑ O'Neill LA. DisSARMing Toll-like receptor signaling. Nat Immunol. 2006 Oct;7(10):1023-5. doi: 10.1038/ni1006-1023. PMID:16985498 doi:http://dx.doi.org/10.1038/ni1006-1023
↑ Peng J, Yuan Q, Lin B, Panneerselvam P, Wang X, Luan XL, Lim SK, Leung BP, Ho B, Ding JL. SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. Eur J Immunol. 2010 Jun;40(6):1738-47. doi: 10.1002/eji.200940034. PMID:20306472 doi:http://dx.doi.org/10.1002/eji.200940034
↑ Wang L, Liu Q, Li S, Wang N, Chen Y, Chen J, Wang L, Huang Y, Sun Z, Dong L, Li S, Liu Q, Gao S, Ma X, Song C, Yang Q. SARM1 senses dsDNA to promote NAD(+) degradation and cell death. Cell. 2025 Oct 24:S0092-8674(25)01126-2. PMID:41138726 doi:10.1016/j.cell.2025.09.026

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9uga"

Categories: Homo sapiens | Large Structures | Wang LN | Yang QK

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9uga is ON HOLD
+==SARM1 senses DNA to promote NAD degradation==
+<StructureSection load='9uga' size='340' side='right'caption='[[9uga]], [[Resolution|resolution]] 3.06&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9uga]] is a 8 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=9UGA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9UGA FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.06&#8491;</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=9uga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9uga OCA], [https://pdbe.org/9uga PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9uga RCSB], [https://www.ebi.ac.uk/pdbsum/9uga PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9uga ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Detection of DNA is a fundamental strategy for life to recognize non-self or abnormal-self to subsequently trigger the downstream responses. However, the mechanism underlying DNA sensing is incompletely understood. Here, we show that a key neural executioner, sterile alpha and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1), senses double-stranded DNA (dsDNA) to promote cell death. dsDNA-bound and -activated SARM1 to degrade nicotinamide adenine dinucleotide (NAD(+)) in a sequence-independent manner. SARM1 bound dsDNA via the TIR domain, and lysine residues in the TIR domain contributed to dsDNA binding. In the cellular context, cytosolic dsDNA from dsDNA transfection or chemotherapy treatment was colocalized with SARM1 and activated SARM1 to elicit NAD(+) degradation and cell death, which was abrogated by SARM1 knockout or DNA-binding residue mutation. Consistently, SARM1 knockout blocked chemotherapy-induced neuropathy (CIN) in mice. Our results reveal SARM1 as a DNA sensor, which might be targetable for therapeutic interventions.
-Authors:
+SARM1 senses dsDNA to promote NAD(+) degradation and cell death.,Wang L, Liu Q, Li S, Wang N, Chen Y, Chen J, Wang L, Huang Y, Sun Z, Dong L, Li S, Liu Q, Gao S, Ma X, Song C, Yang Q Cell. 2025 Oct 24:S0092-8674(25)01126-2. doi: 10.1016/j.cell.2025.09.026. PMID:41138726<ref>PMID:41138726</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9uga" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Wang LN]]
+[[Category: Yang QK]]

9uga

From Proteopedia

Current revision

SARM1 senses DNA to promote NAD degradation

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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