[English] 日本語
Yorodumi
- PDB-8fxs: Crystal structure of human pro-TGF-beta2 in complex with Nb9 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8fxs
TitleCrystal structure of human pro-TGF-beta2 in complex with Nb9
Components
  • Nanobody clone 9
  • Transforming growth factor beta-2 proprotein
KeywordsCYTOKINE / TGF-b TGF-beta nanobody latent procomplex prodomain
Function / homology
Function and homology information


regulation of timing of catagen / regulation of apoptotic process involved in outflow tract morphogenesis / negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / substantia propria of cornea development / ascending aorta morphogenesis / cardioblast differentiation / uterine wall breakdown / positive regulation of timing of catagen / positive regulation of cardioblast differentiation / cardiac right ventricle morphogenesis ...regulation of timing of catagen / regulation of apoptotic process involved in outflow tract morphogenesis / negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / substantia propria of cornea development / ascending aorta morphogenesis / cardioblast differentiation / uterine wall breakdown / positive regulation of timing of catagen / positive regulation of cardioblast differentiation / cardiac right ventricle morphogenesis / regulation of transforming growth factor beta2 production / membranous septum morphogenesis / type III transforming growth factor beta receptor binding / positive regulation of heart contraction / atrial septum morphogenesis / pharyngeal arch artery morphogenesis / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / negative regulation of macrophage cytokine production / signaling / secondary palate development / glial cell migration / somatic stem cell division / TGFBR3 regulates TGF-beta signaling / endocardial cushion fusion / atrial septum primum morphogenesis / positive regulation of integrin biosynthetic process / heart valve morphogenesis / cardiac epithelial to mesenchymal transition / eye development / outflow tract septum morphogenesis / embryonic digestive tract development / positive regulation of stress-activated MAPK cascade / cranial skeletal system development / transforming growth factor beta receptor binding / neural retina development / type II transforming growth factor beta receptor binding / pulmonary valve morphogenesis / ventricular trabecula myocardium morphogenesis / cell-cell junction organization / negative regulation of Ras protein signal transduction / odontogenesis / collagen fibril organization / positive regulation of cell adhesion mediated by integrin / embryo development ending in birth or egg hatching / embryonic limb morphogenesis / Molecules associated with elastic fibres / atrioventricular valve morphogenesis / dopamine biosynthetic process / cardiac muscle cell proliferation / hair follicle morphogenesis / endocardial cushion morphogenesis / activation of protein kinase activity / ventricular septum morphogenesis / generation of neurons / positive regulation of Notch signaling pathway / positive regulation of epithelial cell migration / TGF-beta receptor signaling activates SMADs / uterus development / positive regulation of cell division / positive regulation of SMAD protein signal transduction / inner ear development / hemopoiesis / epithelial to mesenchymal transition / hair follicle development / ECM proteoglycans / neuron development / positive regulation of cell cycle / salivary gland morphogenesis / heart morphogenesis / positive regulation of epithelial to mesenchymal transition / epithelial cell differentiation / extrinsic apoptotic signaling pathway / neutrophil chemotaxis / negative regulation of angiogenesis / transforming growth factor beta receptor signaling pathway / kidney development / platelet alpha granule lumen / skeletal system development / neural tube closure / cytokine activity / response to progesterone / positive regulation of protein secretion / growth factor activity / wound healing / cell morphogenesis / negative regulation of cell growth / positive regulation of miRNA transcription / response to wounding / positive regulation of neuron apoptotic process / male gonad development / negative regulation of epithelial cell proliferation / positive regulation of immune response / cell migration / Platelet degranulation / heart development / amyloid-beta binding / regulation of cell population proliferation / positive regulation of cell growth / collagen-containing extracellular matrix / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Similarity search - Function
Transforming growth factor beta-2 proprotein / Transforming growth factor-beta / TGF-beta, propeptide / TGF-beta propeptide / Transforming growth factor beta, conserved site / TGF-beta family signature. / Transforming growth factor-beta-related / Transforming growth factor-beta (TGF-beta) family / Transforming growth factor-beta, C-terminal / Transforming growth factor beta like domain ...Transforming growth factor beta-2 proprotein / Transforming growth factor-beta / TGF-beta, propeptide / TGF-beta propeptide / Transforming growth factor beta, conserved site / TGF-beta family signature. / Transforming growth factor-beta-related / Transforming growth factor-beta (TGF-beta) family / Transforming growth factor-beta, C-terminal / Transforming growth factor beta like domain / TGF-beta family profile. / Cystine-knot cytokine
Similarity search - Domain/homology
Transforming growth factor beta-2 proprotein
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.15 Å
AuthorsLe, V.Q. / Springer, T.A.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)2R01HL159714 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)1K01DK124443 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)5T32DK007527 United States
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2023
Title: A specialized integrin-binding motif enables proTGF-beta 2 activation by integrin alpha V beta 6 but not alpha V beta 8.
Authors: Le, V.Q. / Zhao, B. / Ramesh, S. / Toohey, C. / DeCosta, A. / Mintseris, J. / Liu, X. / Gygi, S. / Springer, T.A.
History
DepositionJan 25, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 21, 2023Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Transforming growth factor beta-2 proprotein
B: Transforming growth factor beta-2 proprotein
D: Nanobody clone 9
E: Nanobody clone 9
hetero molecules


Theoretical massNumber of molelcules
Total (without water)118,4386
Polymers117,9954
Non-polymers4422
Water724
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area12150 Å2
ΔGint-79 kcal/mol
Surface area42740 Å2
MethodPISA
Unit cell
Length a, b, c (Å)69.683, 89.554, 89.740
Angle α, β, γ (deg.)90.00, 95.00, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Transforming growth factor beta-2 proprotein / Cetermin / Glioblastoma-derived T-cell suppressor factor / G-TSF


Mass: 45195.441 Da / Num. of mol.: 2 / Mutation: C24S, N140R, R298_R303delinsG
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TGFB2 / Variant: Isoform 1 / Cell line (production host): Expi293 GnTI-/- / Production host: Homo sapiens (human) / References: UniProt: P61812
#2: Antibody Nanobody clone 9


Mass: 13802.190 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli BL21(DE3) (bacteria)
#3: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.37 Å3/Da / Density % sol: 48.17 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, hanging drop
Details: Crystals of the Nb9/proTGF-beta2 complex (1 microliter) were formed in hanging drops with 1 microliter of 100 mM HEPES pH 7.6, 10% PEG 4000.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-1 / Wavelength: 0.92009 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Sep 2, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.92009 Å / Relative weight: 1
ReflectionResolution: 3.15→48.27 Å / Num. obs: 18849 / % possible obs: 98.27 % / Redundancy: 3.4 % / CC1/2: 0.967 / Net I/σ(I): 8.48
Reflection shellResolution: 3.15→3.263 Å / Redundancy: 3.6 % / Num. unique obs: 1881 / CC1/2: 0.423 / % possible all: 99.37

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
XDS20190417data reduction
XDS20190417data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.15→48.27 Å / SU ML: 0.54 / Cross valid method: FREE R-VALUE / σ(F): 1.2 / Phase error: 31.24 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.3009 1908 10.12 %
Rwork0.2493 --
obs0.2546 18849 98.3 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.15→48.27 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6706 0 0 4 6710
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.002
X-RAY DIFFRACTIONf_angle_d0.543
X-RAY DIFFRACTIONf_dihedral_angle_d3.935916
X-RAY DIFFRACTIONf_chiral_restr0.043990
X-RAY DIFFRACTIONf_plane_restr0.0051178
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.15-3.230.4031340.3611210X-RAY DIFFRACTION100
3.23-3.320.36851430.32291218X-RAY DIFFRACTION99
3.32-3.410.34481370.29721181X-RAY DIFFRACTION99
3.41-3.520.35081190.28241259X-RAY DIFFRACTION99
3.52-3.650.31411310.27431189X-RAY DIFFRACTION99
3.65-3.80.33271390.28341212X-RAY DIFFRACTION99
3.8-3.970.35531460.3121186X-RAY DIFFRACTION98
3.97-4.180.30821330.23511215X-RAY DIFFRACTION99
4.18-4.440.3021370.20521206X-RAY DIFFRACTION98
4.44-4.780.24511360.20621206X-RAY DIFFRACTION98
4.78-5.260.24321310.21191214X-RAY DIFFRACTION98
5.26-6.020.29591500.25191210X-RAY DIFFRACTION98
6.02-7.580.35651330.27121208X-RAY DIFFRACTION97
7.59-48.270.24911390.22421227X-RAY DIFFRACTION96
Refinement TLS params.Method: refined / Origin x: -17.4657 Å / Origin y: -3.4026 Å / Origin z: 6.9835 Å
111213212223313233
T0.5429 Å2-0.0004 Å20.0129 Å2-0.5895 Å2-0.0083 Å2--0.6622 Å2
L0.5156 °2-0.2331 °20.1056 °2-0.469 °2-0.0942 °2--0.6775 °2
S0.0058 Å °-0.0107 Å °-0.0228 Å °0.0318 Å °-0.0409 Å °-0.0016 Å °0.0188 Å °-0.0132 Å °0.0313 Å °
Refinement TLS groupSelection details: all

+
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://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