[English] 日本語
Yorodumi
- PDB-7ta3: Trimer-to-Monomer Disruption of Tumor Necrosis Factor-alpha (TNF-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ta3
TitleTrimer-to-Monomer Disruption of Tumor Necrosis Factor-alpha (TNF-alpha) by alpha-peptide-3
Components
  • Alpha-peptide-3
  • Tumor necrosis factor
KeywordsSIGNALING PROTEIN / tumor necrosis factor-alpha / signaling
Function / homology
Function and homology information


negative regulation of L-glutamate import across plasma membrane / negative regulation of bile acid secretion / response to Gram-negative bacterium / positive regulation of neutrophil activation / negative regulation of branching involved in lung morphogenesis / positive regulation of interleukin-33 production / positive regulation of blood microparticle formation / positive regulation of chronic inflammatory response to antigenic stimulus / positive regulation of fractalkine production / : ...negative regulation of L-glutamate import across plasma membrane / negative regulation of bile acid secretion / response to Gram-negative bacterium / positive regulation of neutrophil activation / negative regulation of branching involved in lung morphogenesis / positive regulation of interleukin-33 production / positive regulation of blood microparticle formation / positive regulation of chronic inflammatory response to antigenic stimulus / positive regulation of fractalkine production / : / positive regulation of vitamin D biosynthetic process / response to macrophage colony-stimulating factor / positive regulation of leukocyte adhesion to arterial endothelial cell / positive regulation of translational initiation by iron / response to 3,3',5-triiodo-L-thyronine / regulation of membrane lipid metabolic process / regulation of endothelial cell apoptotic process / regulation of branching involved in salivary gland morphogenesis / chronic inflammatory response to antigenic stimulus / negative regulation of protein-containing complex disassembly / response to gold nanoparticle / positive regulation of humoral immune response mediated by circulating immunoglobulin / negative regulation of myosin-light-chain-phosphatase activity / positive regulation of hair follicle development / negative regulation of myelination / death receptor agonist activity / response to isolation stress / negative regulation of vascular wound healing / negative regulation of bicellular tight junction assembly / negative regulation of amyloid-beta clearance / negative regulation of cytokine production involved in immune response / inflammatory response to wounding / cellular response to toxic substance / positive regulation of calcidiol 1-monooxygenase activity / positive regulation of I-kappaB phosphorylation / sequestering of triglyceride / positive regulation of interleukin-18 production / positive regulation of action potential / TNF signaling / positive regulation of protein transport / epithelial cell proliferation involved in salivary gland morphogenesis / toll-like receptor 3 signaling pathway / embryonic digestive tract development / positive regulation of superoxide dismutase activity / leukocyte migration involved in inflammatory response / necroptotic signaling pathway / vascular endothelial growth factor production / positive regulation of calcineurin-NFAT signaling cascade / positive regulation of neuroinflammatory response / leukocyte tethering or rolling / positive regulation of synoviocyte proliferation / response to fructose / positive regulation of fever generation / positive regulation of mononuclear cell migration / negative regulation of myoblast differentiation / negative regulation of glucose import / regulation of establishment of endothelial barrier / endothelial cell apoptotic process / macrophage activation involved in immune response / positive regulation of protein localization to cell surface / TNFR1-mediated ceramide production / negative regulation of oxidative phosphorylation / positive regulation of osteoclast differentiation / positive regulation of cytokine production involved in inflammatory response / tumor necrosis factor receptor binding / negative regulation of systemic arterial blood pressure / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of programmed cell death / regulation of immunoglobulin production / positive regulation of hepatocyte proliferation / positive regulation of heterotypic cell-cell adhesion / positive regulation of protein-containing complex disassembly / positive regulation of podosome assembly / positive regulation of membrane protein ectodomain proteolysis / regulation of canonical NF-kappaB signal transduction / regulation of reactive oxygen species metabolic process / TNFR1-induced proapoptotic signaling / regulation of fat cell differentiation / positive regulation of leukocyte adhesion to vascular endothelial cell / response to L-glutamate / cortical actin cytoskeleton organization / negative regulation of heart rate / positive regulation of amyloid-beta formation / positive regulation of DNA biosynthetic process / negative regulation of viral genome replication / regulation of synapse organization / negative regulation of fat cell differentiation / negative regulation of endothelial cell proliferation / Interleukin-10 signaling / regulation of insulin secretion / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of interleukin-6 production / phagocytic cup / antiviral innate immune response / negative regulation of apoptotic signaling pathway / humoral immune response / negative regulation of blood vessel endothelial cell migration / negative regulation of lipid storage / skeletal muscle contraction
Similarity search - Function
Tumour necrosis factor alpha / Tumour necrosis factor / Tumour necrosis factor, conserved site / Tumor necrosis factor (TNF) homology domain (THD) signature. / Tumour necrosis factor family. / TNF(Tumour Necrosis Factor) family / Tumour necrosis factor domain / Tumor necrosis factor (TNF) homology domain (THD) profile. / Tumour necrosis factor-like domain superfamily
Similarity search - Domain/homology
Tumor necrosis factor
Similarity search - Component
Biological speciesHomo sapiens (human)
Synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsNiu, J. / Bingman, C.A. / Gellman, S.H.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01-GM056414 United States
CitationJournal: J.Am.Chem.Soc. / Year: 2022
Title: Trimer-to-Monomer Disruption Mechanism for a Potent, Protease-Resistant Antagonist of Tumor Necrosis Factor-alpha Signaling.
Authors: Niu, J. / Cederstrand, A.J. / Eddinger, G.A. / Yin, B. / Checco, J.W. / Bingman, C.A. / Outlaw, V.K. / Gellman, S.H.
History
DepositionDec 20, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 29, 2022Provider: repository / Type: Initial release
Revision 1.1Apr 3, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Alpha-peptide-3
B: Tumor necrosis factor
C: Alpha-peptide-3
D: Tumor necrosis factor


Theoretical massNumber of molelcules
Total (without water)42,1244
Polymers42,1244
Non-polymers00
Water23413
1
A: Alpha-peptide-3
B: Tumor necrosis factor


Theoretical massNumber of molelcules
Total (without water)21,0622
Polymers21,0622
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1920 Å2
ΔGint-13 kcal/mol
Surface area9460 Å2
MethodPISA
2
C: Alpha-peptide-3
D: Tumor necrosis factor


Theoretical massNumber of molelcules
Total (without water)21,0622
Polymers21,0622
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)86.560, 86.560, 143.730
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212

-
Components

#1: Protein/peptide Alpha-peptide-3


Mass: 3604.020 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Synthetic construct (others)
#2: Protein Tumor necrosis factor / Cachectin / TNF-alpha / Tumor necrosis factor ligand superfamily member 2 / TNF-a


Mass: 17457.736 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TNF, TNFA, TNFSF2 / Production host: Escherichia coli (E. coli) / References: UniProt: P01375
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 13 / 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: 3.2 Å3/Da / Density % sol: 61.51 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 8.5
Details: 1.5M ammonium sulfate, 0.1 M tris HCL pH 8.5, 12% glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.12713 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Oct 18, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.12713 Å / Relative weight: 1
ReflectionResolution: 2.5→43.28 Å / Num. obs: 19636 / % possible obs: 99.9 % / Redundancy: 26.4 % / Biso Wilson estimate: 69.58 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.111 / Rrim(I) all: 0.113 / Χ2: 1.046 / Net I/σ(I): 20.51 / Num. measured all: 518383 / Scaling rejects: 24
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
2.5-2.5726.5431.851.4637770142314230.8681.886100
2.57-2.6427.91.5071.9838251137213710.931.53599.9
2.64-2.7127.7941.0682.9837856136213620.9571.087100
2.71-2.827.7120.9173.5536331131113110.9760.934100
2.8-2.8927.5990.8074.235216127612760.9710.822100
2.89-2.9927.3280.5585.9333422122312230.9860.568100
2.99-3.127.0310.4248.0432005118411840.9920.432100
3.1-3.2326.5870.30710.9430814116011590.9940.31399.9
3.23-3.3726.0450.21614.9228519109510950.9960.221100
3.37-3.5423.5290.16519.3124658105110480.9970.16999.7
3.54-3.7325.5260.11726.9626088102210220.9980.119100
3.73-3.9527.5750.10632.05266939689680.9990.108100
3.95-4.2327.130.08140.97246079079070.9990.083100
4.23-4.5626.820.06550.07228248518510.9990.067100
4.56-526.1630.06150.372043378178110.063100
5-5.5925.5740.06647.38186697307300.9990.067100
5.59-6.4623.5930.06546.71151706436430.9990.067100
6.46-7.9122.1360.05252.72122415585530.9990.05499.1
7.91-11.1825.1880.03969.031136045145110.04100
11.18-43.2819.6260.04254.84545628627810.04397.2

-
Processing

Software
NameVersionClassification
XDSMar 15, 2019data reduction
XSCALEMar 15, 2019data scaling
PHENIX1.19.2refinement
PDB_EXTRACT3.27data extraction
PHASER2.8.3phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1TNF_A

Resolution: 2.5→43.28 Å / SU ML: 0.34 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 34.39 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2767 1934 9.91 %
Rwork0.2459 17589 -
obs0.249 19523 99.66 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 226.36 Å2 / Biso mean: 98.6984 Å2 / Biso min: 54.84 Å2
Refinement stepCycle: final / Resolution: 2.5→43.28 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2758 0 0 13 2771
Biso mean---70.55 -
Num. residues----355
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.5-2.560.4495950.40031267136299
2.56-2.630.39241930.36261150134399
2.63-2.710.3711970.338512891386100
2.71-2.80.33611920.33111162135499
2.8-2.90.4371970.342712711368100
2.9-3.010.383960.33521260135699
3.01-3.150.36271940.301911891383100
3.15-3.320.3228970.287112841381100
3.32-3.520.31221940.260511891383100
3.52-3.80.3126970.241413051402100
3.8-4.180.25671460.218212601406100
4.18-4.780.24571450.184312761421100
4.78-6.020.2541970.223213401437100
6.02-43.280.21641940.23561347154199
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.36590.1530.21980.17670.11070.18390.1323-0.3429-0.266-0.96350.10760.8336-1.9939-0.1370.00291.1050.04960.02280.8479-0.05560.8658-6.034-52.6812-21.6957
20.0480.00660.00250.0216-0.0433-0.0270.6824-0.35241.04820.7463-1.5802-1.2599-0.9290.8144-0.00460.9555-0.0626-0.14951.12960.09480.9885.3481-58.0916-25.0202
31.40151.48230.71382.1533-0.15581.31620.00480.8676-0.06361.4804-0.3688-0.8416-0.5271-0.6037-0.0021.1211-0.1427-0.1090.71870.00630.8525-1.122-60.1081-15.204
41.52740.009-0.48784.0166-0.10782.81360.06620.1488-0.19920.00920.01480.0050.0111-0.0519-00.6535-0.03110.00350.6277-0.0570.7299-10.4588-65.3435-28.1643
54.04690.41650.80950.32350.24632.60910.0609-0.3789-0.22230.60720.0867-0.67840.2138-0.549-0.00040.7672-0.02130.08550.6617-0.04180.7014-21.7684-67.96-21.5036
63.4908-1.97510.692.2345-0.78492.20630.07420.08170.18330.1883-0.0586-0.0510.0042-0.22730.00040.7915-0.02670.03960.6297-0.03330.6935-15.798-60.2568-25.6709
70.32330.32420.26851.0746-0.10540.45780.9762-0.3985-1.70340.26250.35190.63430.39460.1769-0.00080.95510.0397-0.04010.8278-0.06161.0047-36.9646-86.7105-9.9183
80.27620.0590.0160.2834-0.16580.22420.94-0.19351.04921.40850.501-0.3926-1.19530.7529-0.00310.9437-0.17010.22541.7993-0.08240.919-44.9213-84.1321-0.2023
91.25241.3030.78981.75-0.36941.41580.6828-0.93840.21140.8982-0.0988-0.37380.1747-0.73520.00181.1149-0.15950.08790.8634-0.02020.7838-33.5327-80.1104-2.1138
102.891-0.4637-0.88262.6364-1.68031.29460.52610.12230.25160.31980.04150.7871-0.6918-0.6516-0.00360.82430.0410.15370.77270.03570.9223-44.7802-75.4036-14.8067
110.12410.11450.30590.35120.36210.76511.2017-0.6093-0.35070.2742-0.41631.98141.1248-1.7030.03051.049-0.01430.09041.2202-0.02731.4571-48.0191-75.9643-10.0836
121.2041.7853-0.941.8889-0.33981.00450.088-0.22830.3863-0.27930.17110.679-0.6965-0.016100.85390.12220.09160.7659-0.06520.8006-38.3854-71.0884-13.452
131.48571.9220.04951.1094-0.28062.7251-0.00310.20630.2210.2030.11270.3880.0078-0.20470.00040.71280.01570.05470.63860.02160.7482-32.0885-73.6458-26.0177
140.9416-0.00550.06990.2867-0.35640.3288-1.00250.5195-0.2636-1.05220.2469-0.71640.6290.39380.00071.3333-0.02670.040.9410.05680.9682-29.4119-94.3526-36.4386
150.5234-0.9125-1.25421.47210.80381.10120.13040.0320.3421-0.1541-0.19480.5033-0.0022-0.4046-0.00020.87060.00910.03390.77940.01360.7929-36.501-76.9438-18.5186
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 1 through 10 )A1 - 10
2X-RAY DIFFRACTION2chain 'A' and (resid 11 through 16 )A11 - 16
3X-RAY DIFFRACTION3chain 'A' and (resid 17 through 31 )A17 - 31
4X-RAY DIFFRACTION4chain 'B' and (resid 8 through 74 )B8 - 74
5X-RAY DIFFRACTION5chain 'B' and (resid 75 through 99 )B75 - 99
6X-RAY DIFFRACTION6chain 'B' and (resid 100 through 157 )B100 - 157
7X-RAY DIFFRACTION7chain 'C' and (resid 1 through 11 )C1 - 11
8X-RAY DIFFRACTION8chain 'C' and (resid 12 through 16 )C12 - 16
9X-RAY DIFFRACTION9chain 'C' and (resid 17 through 31 )C17 - 31
10X-RAY DIFFRACTION10chain 'D' and (resid 9 through 27 )D9 - 27
11X-RAY DIFFRACTION11chain 'D' and (resid 28 through 38 )D28 - 38
12X-RAY DIFFRACTION12chain 'D' and (resid 39 through 66 )D39 - 66
13X-RAY DIFFRACTION13chain 'D' and (resid 67 through 98 )D67 - 98
14X-RAY DIFFRACTION14chain 'D' and (resid 99 through 113 )D99 - 113
15X-RAY DIFFRACTION15chain 'D' and (resid 114 through 157 )D114 - 157

+
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