[English] 日本語
Yorodumi
- PDB-7lcz: Crystal structure of the ARM domain from Drosophila SARM1 in comp... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7lcz
TitleCrystal structure of the ARM domain from Drosophila SARM1 in complex with NMN
ComponentsIsoform B of NAD(+) hydrolase sarm1
KeywordsHYDROLASE / NADase / Autoinhibition / ARM domain / Allostery / SIGNALING PROTEIN
Function / homology
Function and homology information


negative regulation of MyD88-independent toll-like receptor signaling pathway / positive regulation of receptor signaling pathway via STAT / NAD catabolic process / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / NAD+ nucleosidase activity / NAD+ nucleotidase, cyclic ADP-ribose generating / STAT family protein binding / antiviral innate immune response / response to axon injury / signaling adaptor activity ...negative regulation of MyD88-independent toll-like receptor signaling pathway / positive regulation of receptor signaling pathway via STAT / NAD catabolic process / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / NAD+ nucleosidase activity / NAD+ nucleotidase, cyclic ADP-ribose generating / STAT family protein binding / antiviral innate immune response / response to axon injury / signaling adaptor activity / defense response to virus / neuron projection / axon / neuronal cell body / dendrite / signal transduction / cytosol
Similarity search - Function
Sterile alpha and TIR motif-containing protein 1 / TIR domain / Toll - interleukin 1 - resistance / TIR domain profile. / Toll/interleukin-1 receptor homology (TIR) domain / Toll/interleukin-1 receptor homology (TIR) domain superfamily / SAM domain (Sterile alpha motif) / SAM domain profile. / Sterile alpha motif. / Sterile alpha motif domain ...Sterile alpha and TIR motif-containing protein 1 / TIR domain / Toll - interleukin 1 - resistance / TIR domain profile. / Toll/interleukin-1 receptor homology (TIR) domain / Toll/interleukin-1 receptor homology (TIR) domain superfamily / SAM domain (Sterile alpha motif) / SAM domain profile. / Sterile alpha motif. / Sterile alpha motif domain / Sterile alpha motif/pointed domain superfamily / Armadillo-like helical / Armadillo-type fold
Similarity search - Domain/homology
BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE / NAD(+) hydrolase sarm1
Similarity search - Component
Biological speciesDrosophila melanogaster (fruit fly)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MIRAS / Resolution: 1.65 Å
AuthorsGu, W. / Nanson, J.D. / Luo, Z. / Jia, X. / Manik, M.K. / Ve, T. / Kobe, B.
Funding support Australia, 6items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)1107804 Australia
National Health and Medical Research Council (NHMRC, Australia)1160570 Australia
National Health and Medical Research Council (NHMRC, Australia)1071659 Australia
National Health and Medical Research Council (NHMRC, Australia)1108859 Australia
Australian Research Council (ARC)FL180100109 Australia
Australian Research Council (ARC)DE170100783 Australia
CitationJournal: Neuron / Year: 2021
Title: SARM1 is a metabolic sensor activated by an increased NMN/NAD ratio to trigger axon degeneration.
Authors: Matthew D Figley / Weixi Gu / Jeffrey D Nanson / Yun Shi / Yo Sasaki / Katie Cunnea / Alpeshkumar K Malde / Xinying Jia / Zhenyao Luo / Forhad K Saikot / Tamim Mosaiab / Veronika Masic / ...Authors: Matthew D Figley / Weixi Gu / Jeffrey D Nanson / Yun Shi / Yo Sasaki / Katie Cunnea / Alpeshkumar K Malde / Xinying Jia / Zhenyao Luo / Forhad K Saikot / Tamim Mosaiab / Veronika Masic / Stephanie Holt / Lauren Hartley-Tassell / Helen Y McGuinness / Mohammad K Manik / Todd Bosanac / Michael J Landsberg / Philip S Kerry / Mehdi Mobli / Robert O Hughes / Jeffrey Milbrandt / Bostjan Kobe / Aaron DiAntonio / Thomas Ve /
Abstract: Axon degeneration is a central pathological feature of many neurodegenerative diseases. Sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) is a nicotinamide adenine dinucleotide ...Axon degeneration is a central pathological feature of many neurodegenerative diseases. Sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD)-cleaving enzyme whose activation triggers axon destruction. Loss of the biosynthetic enzyme NMNAT2, which converts nicotinamide mononucleotide (NMN) to NAD, activates SARM1 via an unknown mechanism. Using structural, biochemical, biophysical, and cellular assays, we demonstrate that SARM1 is activated by an increase in the ratio of NMN to NAD and show that both metabolites compete for binding to the auto-inhibitory N-terminal armadillo repeat (ARM) domain of SARM1. We report structures of the SARM1 ARM domain bound to NMN and of the homo-octameric SARM1 complex in the absence of ligands. We show that NMN influences the structure of SARM1 and demonstrate via mutagenesis that NMN binding is required for injury-induced SARM1 activation and axon destruction. Hence, SARM1 is a metabolic sensor responding to an increased NMN/NAD ratio by cleaving residual NAD, thereby inducing feedforward metabolic catastrophe and axonal demise.
History
DepositionJan 12, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 10, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 17, 2021Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Apr 21, 2021Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first
Revision 1.3Mar 6, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform B of NAD(+) hydrolase sarm1
B: Isoform B of NAD(+) hydrolase sarm1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)69,39010
Polymers68,5422
Non-polymers8478
Water10,737596
1
A: Isoform B of NAD(+) hydrolase sarm1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,7155
Polymers34,2711
Non-polymers4434
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Isoform B of NAD(+) hydrolase sarm1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,6755
Polymers34,2711
Non-polymers4044
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)38.921, 50.788, 76.054
Angle α, β, γ (deg.)103.516, 101.899, 95.261
Int Tables number1
Space group name H-MP1
Space group name HallP1
Symmetry operation#1: x,y,z

-
Components

#1: Protein Isoform B of NAD(+) hydrolase sarm1 / NADase sarm1 / Sterile alpha and TIR motif-containing protein 1 / Tir-1 homolog


Mass: 34271.234 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Drosophila melanogaster (fruit fly) / Gene: Sarm, Ect4, CG43119 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q6IDD9, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase
#2: Chemical ChemComp-NMN / BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE / NICOTINAMIDE MONONUCLEOTIDE


Mass: 335.227 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C11H16N2O8P / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical
ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: Na
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 596 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.06 Å3/Da / Density % sol: 40.41 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 0.1 M SPG buffer (pH 8.0) and 25% PEG1500

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.95372 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: May 4, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.95372 Å / Relative weight: 1
ReflectionResolution: 1.46→71.88 Å / Num. obs: 83026 / % possible obs: 83.5 % / Redundancy: 7.1 % / Biso Wilson estimate: 19.54 Å2 / CC1/2: 0.999 / Net I/σ(I): 15.9
Reflection shellResolution: 1.46→1.6 Å / Num. unique obs: 3201 / CC1/2: 0.633

-
Processing

Software
NameVersionClassification
PHENIX1.19rc4_4035refinement
autoSHARPphasing
Cootmodel building
BUCCANEERmodel building
XDSdata reduction
Aimlessdata scaling
RefinementMethod to determine structure: MIRAS / Resolution: 1.65→37.67 Å / SU ML: 0.1983 / Cross valid method: FREE R-VALUE / σ(F): 1.96 / Phase error: 25.611
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2295 3551 3.11 %
Rwork0.212 110546 -
obs0.2125 57342 86.5 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 27.77 Å2
Refinement stepCycle: LAST / Resolution: 1.65→37.67 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4724 0 53 596 5373
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00254984
X-RAY DIFFRACTIONf_angle_d0.47326764
X-RAY DIFFRACTIONf_chiral_restr0.0322768
X-RAY DIFFRACTIONf_plane_restr0.0034880
X-RAY DIFFRACTIONf_dihedral_angle_d11.26831871
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.65-1.690.29491690.325957X-RAY DIFFRACTION69.38
1.69-1.730.28962090.30616352X-RAY DIFFRACTION75.6
1.73-1.780.28952330.30427203X-RAY DIFFRACTION83.78
1.78-1.830.30562210.2947584X-RAY DIFFRACTION88.75
1.83-1.890.31912870.28057891X-RAY DIFFRACTION93.42
1.89-1.960.28891480.27515335X-RAY DIFFRACTION61.76
1.96-2.030.30032740.25828142X-RAY DIFFRACTION95.96
2.03-2.130.26111820.24555964X-RAY DIFFRACTION70.35
2.13-2.240.24042960.23038173X-RAY DIFFRACTION95.91
2.24-2.380.21162210.2277350X-RAY DIFFRACTION86.51
2.38-2.560.24852720.21758273X-RAY DIFFRACTION96.71
2.56-2.820.2842340.21167355X-RAY DIFFRACTION86.53
2.82-3.230.19542680.20158327X-RAY DIFFRACTION97.16
3.23-4.070.2082720.17098302X-RAY DIFFRACTION98.12
4.07-37.670.17152650.16688338X-RAY DIFFRACTION97.63

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more