+Open data
-Basic information
Entry | Database: PDB / ID: 7anw | ||||||
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Title | hSARM1 NAD+ complex | ||||||
Components | NAD(+) hydrolase SARM1 | ||||||
Keywords | APOPTOSIS / NADase / ARM domain / SAM domain / TIR domain | ||||||
Function / homology | Function and homology information negative regulation of MyD88-independent toll-like receptor signaling pathway / MyD88-independent TLR4 cascade / Toll Like Receptor 3 (TLR3) Cascade / NADP+ nucleosidase activity / NAD catabolic process / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / NAD+ nucleosidase activity / protein localization to mitochondrion / NAD+ nucleotidase, cyclic ADP-ribose generating / nervous system process ...negative regulation of MyD88-independent toll-like receptor signaling pathway / MyD88-independent TLR4 cascade / Toll Like Receptor 3 (TLR3) Cascade / NADP+ nucleosidase activity / NAD catabolic process / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / NAD+ nucleosidase activity / protein localization to mitochondrion / NAD+ nucleotidase, cyclic ADP-ribose generating / nervous system process / Hydrolases; Glycosylases; Hydrolysing N-glycosyl compounds / regulation of dendrite morphogenesis / response to axon injury / regulation of neuron apoptotic process / response to glucose / signaling adaptor activity / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / IKK complex recruitment mediated by RIP1 / nervous system development / mitochondrial outer membrane / microtubule / cell differentiation / axon / innate immune response / dendrite / synapse / cell surface / signal transduction / protein-containing complex / mitochondrion / identical protein binding / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.68 Å | ||||||
Authors | Sporny, M. / Guez-Haddad, J. / Khazma, T. / Yaron, A. / Mim, C. / Isupov, M.N. / Zalk, R. / Dessau, M. / Hons, M. / Opatowsky, Y. | ||||||
Funding support | Israel, 1items
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Citation | Journal: Elife / Year: 2020 Title: Structural basis for SARM1 inhibition and activation under energetic stress. Authors: Michael Sporny / Julia Guez-Haddad / Tami Khazma / Avraham Yaron / Moshe Dessau / Yoel Shkolnisky / Carsten Mim / Michail N Isupov / Ran Zalk / Michael Hons / Yarden Opatowsky / Abstract: SARM1, an executor of axonal degeneration, displays NADase activity that depletes the key cellular metabolite, NAD+, in response to nerve injury. The basis of SARM1 inhibition and its activation ...SARM1, an executor of axonal degeneration, displays NADase activity that depletes the key cellular metabolite, NAD+, in response to nerve injury. The basis of SARM1 inhibition and its activation under stress conditions are still unknown. Here, we present cryo-EM maps of SARM1 at 2.9 and 2.7 Å resolutions. These indicate that SARM1 homo-octamer avoids premature activation by assuming a packed conformation, with ordered inner and peripheral rings, that prevents dimerization and activation of the catalytic domains. This inactive conformation is stabilized by binding of SARM1's own substrate NAD+ in an allosteric location, away from the catalytic sites. This model was validated by mutagenesis of the allosteric site, which led to constitutively active SARM1. We propose that the reduction of cellular NAD+ concentration contributes to the disassembly of SARM1's peripheral ring, which allows formation of active NADase domain dimers, thereby further depleting NAD+ to cause an energetic catastrophe and cell death. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7anw.cif.gz | 980.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7anw.ent.gz | 820.2 KB | Display | PDB format |
PDBx/mmJSON format | 7anw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7anw_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7anw_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 7anw_validation.xml.gz | 129.8 KB | Display | |
Data in CIF | 7anw_validation.cif.gz | 199.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/an/7anw ftp://data.pdbj.org/pub/pdb/validation_reports/an/7anw | HTTPS FTP |
-Related structure data
Related structure data | 11834MC 6zfxC 6zg0C 6zg1C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Beg auth comp-ID: GLY / Beg label comp-ID: GLY / End auth comp-ID: GLN / End label comp-ID: GLN / Refine code: _ / Auth seq-ID: 56 - 700 / Label seq-ID: 57 - 701
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