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- EMDB-17369: A CHIMERA construct containing human SARM1 ARM and SAM domains an... -
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Open data
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Basic information
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Title | A CHIMERA construct containing human SARM1 ARM and SAM domains and C. elegans TIR domain. | ||||||||||||
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![]() | SARM1 / TIR-1 / C. elegans / neurodegeneration / cryo-EM / structural biology / NAD+ metabolism / axon Wallerian degeneration / HYDROLASE | ||||||||||||
Function / homology | ![]() serotonin biosynthetic 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 ...serotonin biosynthetic 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 / cell fate specification / Hydrolases; Glycosylases; Hydrolysing N-glycosyl compounds / regulation of dendrite morphogenesis / response to axon injury / defense response to fungus / regulation of neuron apoptotic process / response to glucose / signaling adaptor activity / axon cytoplasm / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / IKK complex recruitment mediated by RIP1 / protein localization / small GTPase binding / cell-cell signaling / nervous system development / cell body / defense response to Gram-negative bacterium / microtubule / mitochondrial outer membrane / cell differentiation / defense response to bacterium / axon / negative regulation of gene expression / innate immune response / synapse / dendrite / positive regulation of gene expression / protein kinase binding / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / identical protein binding / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.68 Å | ||||||||||||
![]() | Isupov MN / Opatowsky Y | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structure-function analysis of ceTIR-1/hSARM1 explains the lack of Wallerian axonal degeneration in C. elegans. Authors: Tami Khazma / Atira Grossman / Julia Guez-Haddad / Chengye Feng / Hadas Dabas / Radhika Sain / Michal Weitman / Ran Zalk / Michail N Isupov / Marc Hammarlund / Michael Hons / Yarden Opatowsky / ![]() ![]() ![]() ![]() Abstract: Wallerian axonal degeneration (WD) does not occur in the nematode C. elegans, in contrast to other model animals. However, WD depends on the NADase activity of SARM1, a protein that is also expressed ...Wallerian axonal degeneration (WD) does not occur in the nematode C. elegans, in contrast to other model animals. However, WD depends on the NADase activity of SARM1, a protein that is also expressed in C. elegans (ceSARM/ceTIR-1). We hypothesized that differences in SARM between species might exist and account for the divergence in WD. We first show that expression of the human (h)SARM1, but not ceTIR-1, in C. elegans neurons is sufficient to confer axon degeneration after nerve injury. Next, we determined the cryoelectron microscopy structure of ceTIR-1 and found that, unlike hSARM1, which exists as an auto-inhibited ring octamer, ceTIR-1 forms a readily active 9-mer. Enzymatically, the NADase activity of ceTIR-1 is substantially weaker (10-fold higher Km) than that of hSARM1, and even when fully active, it falls short of consuming all cellular NAD. Our experiments provide insight into the molecular mechanisms and evolution of SARM orthologs and WD across species. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 51.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.1 KB 17.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.9 KB | Display | ![]() |
Images | ![]() | 98.8 KB | ||
Others | ![]() ![]() | 95.5 MB 95.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 924 KB | Display | ![]() |
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Full document | ![]() | 923.6 KB | Display | |
Data in XML | ![]() | 18.2 KB | Display | |
Data in CIF | ![]() | 23.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8p2lMC ![]() 8p2mC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.84 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_17369_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_17369_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : A CHIMERA construct containing human SARM1 ARM and SAM domains an...
Entire | Name: A CHIMERA construct containing human SARM1 ARM and SAM domains and C. elegans TIR domain. |
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Components |
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-Supramolecule #1: A CHIMERA construct containing human SARM1 ARM and SAM domains an...
Supramolecule | Name: A CHIMERA construct containing human SARM1 ARM and SAM domains and C. elegans TIR domain. type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: NAD(+) hydrolase SARM1,NAD(+) hydrolase tir-1
Macromolecule | Name: NAD(+) hydrolase SARM1,NAD(+) hydrolase tir-1 / type: protein_or_peptide / ID: 1 / Number of copies: 16 / Enantiomer: LEVO / EC number: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 81.070656 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSYHHHHHHD YDIPTTENLY FQGAMGSERL AVPGPDGGGG TGPWWAAGGR GPREVSPGAG TEVQDALERA LPELQQALSA LKQAGGARA VGAGLAEVFQ LVEEAWLLPA VGREVAQGLC DAIRLDGGLD LLLRLLQAPE LETRVQAARL LEQILVAENR D RVARIGLG ...String: MSYHHHHHHD YDIPTTENLY FQGAMGSERL AVPGPDGGGG TGPWWAAGGR GPREVSPGAG TEVQDALERA LPELQQALSA LKQAGGARA VGAGLAEVFQ LVEEAWLLPA VGREVAQGLC DAIRLDGGLD LLLRLLQAPE LETRVQAARL LEQILVAENR D RVARIGLG VILNLAKERE PVELARSVAG ILEHMFKHSE ETCQRLVAAG GLDAVLYWCR RTDPALLRHC ALALGNCALH GG QAVQRRM VEKRAAEWLF PLAFSKEDEL LRLHACLAVA VLATNKEVER EVERSGTLAL VEPLVASLDP GRFARCLVDA SDT SQGRGP DDLQRLVPLL DSNRLEAQCI GAFYLCAEAA IKSLQGKTKV FSDIGAIQSL KRLVSYSTNG TKSALAKRAL RLLG EEVPR PILPSVPSWK EAEVQTWLQQ IGFSKYCESF REQQVDGDLL LRLTEEELQT DLGMKSGITR KRFFRELTEL KTFAN YSTC DRSNLADWLG SLDPRFRQYT YGLVSCGLDR SLLHRVSEQQ LLEDCGIHLG VHRARILTAA REMLHSPLPC TGGKPS GDT PDVFISYRRS TGNQLASLIK VLLQLRGYRV FIDVDKLYAG KFDSSLLKNI QAAKHFILVL TPNSLDRLLN DDNCEDW VH KELKCAFEHQ KNIIPIFDTA FEFPTKEDQI PNDIRMITKY NGVKWVHDYQ DACMAKVVRF ITGELNRTTP TTKEMPSI S RKTTQQR UniProtKB: NAD(+) hydrolase SARM1, NAD(+) hydrolase tir-1 |
-Macromolecule #2: NICOTINAMIDE-ADENINE-DINUCLEOTIDE
Macromolecule | Name: NICOTINAMIDE-ADENINE-DINUCLEOTIDE / type: ligand / ID: 2 / Number of copies: 8 / Formula: NAD |
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Molecular weight | Theoretical: 663.425 Da |
Chemical component information | ![]() ChemComp-NAD: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8.5 |
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Grid | Model: Quantifoil R1.2/1.3 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Specialist optics | Energy filter - Name: GIF Quantum LS |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 41.4 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Space: RECIPROCAL / Protocol: FLEXIBLE FIT | |||||||||
Output model | ![]() PDB-8p2l: |