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Open data
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Basic information
Entry | Database: PDB / ID: 7cm5 | ||||||
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Title | Full-length Sarm1 in a self-inhibited state | ||||||
![]() | NAD(+) hydrolase SARM1 | ||||||
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Function / homology | ![]() negative regulation of MyD88-independent toll-like receptor signaling pathway / MyD88-independent TLR4 cascade / Toll Like Receptor 3 (TLR3) Cascade / NAD catabolic process / NADP+ nucleosidase activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Zhang, Z. / Jiang, Y. | ||||||
![]() | ![]() Title: The NAD-mediated self-inhibition mechanism of pro-neurodegenerative SARM1. Authors: Yuefeng Jiang / Tingting Liu / Chia-Hsueh Lee / Qing Chang / Jing Yang / Zhe Zhang / ![]() ![]() Abstract: Pathological degeneration of axons disrupts neural circuits and represents one of the hallmarks of neurodegeneration. Sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 (SARM1) ...Pathological degeneration of axons disrupts neural circuits and represents one of the hallmarks of neurodegeneration. Sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 (SARM1) is a central regulator of this neurodegenerative process, and its Toll/interleukin-1 receptor (TIR) domain exerts its pro-neurodegenerative action through NADase activity. However, the mechanisms by which the activation of SARM1 is stringently controlled are unclear. Here we report the cryo-electron microscopy structures of full-length SARM1 proteins. We show that NAD is an unexpected ligand of the armadillo/heat repeat motifs (ARM) domain of SARM1. This binding of NAD to the ARM domain facilitated the inhibition of the TIR-domain NADase through the domain interface. Disruption of the NAD-binding site or the ARM-TIR interaction caused constitutive activation of SARM1 and thereby led to axonal degeneration. These findings suggest that NAD mediates self-inhibition of this central pro-neurodegenerative protein. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 811.2 KB | Display | ![]() |
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PDB format | ![]() | 682.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 30401MC ![]() 7cm6C ![]() 7cm7C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 80504.289 Da / Num. of mol.: 8 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q6SZW1, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase, ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Octamer of full-length Sarm1 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 640 kDa/nm / Experimental value: YES |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 57.5 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
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EM software |
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CTF correction![]() | Type: NONE | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 615638 | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 214494 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: GeoStd + Monomer Library | ||||||||||||||||||||||||
Refine LS restraints |
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