[English] 日本語
Yorodumi
- EMDB-33571: Human L-TGF-beta1 in complex with the anchor protein LRRC33 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-33571
TitleHuman L-TGF-beta1 in complex with the anchor protein LRRC33
Map data
Sample
  • Complex: L-TGF-beta1 in complex with its anchor protein LRRC33
    • Protein or peptide: Transforming growth factor beta-1 proprotein
    • Protein or peptide: Transforming growth factor beta activator LRRC33
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Function / homology
Function and homology information


: / sequestering of TGFbeta in extracellular matrix / positive regulation of primary miRNA processing / positive regulation of microglia differentiation / Influenza Virus Induced Apoptosis / negative regulation of skeletal muscle tissue development / TGFBR2 MSI Frameshift Mutants in Cancer / regulatory T cell differentiation / regulation of blood vessel remodeling / regulation of striated muscle tissue development ...: / sequestering of TGFbeta in extracellular matrix / positive regulation of primary miRNA processing / positive regulation of microglia differentiation / Influenza Virus Induced Apoptosis / negative regulation of skeletal muscle tissue development / TGFBR2 MSI Frameshift Mutants in Cancer / regulatory T cell differentiation / regulation of blood vessel remodeling / regulation of striated muscle tissue development / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / regulation of protein import into nucleus / extracellular matrix assembly / embryonic liver development / type III transforming growth factor beta receptor binding / negative regulation of hyaluronan biosynthetic process / positive regulation of cardiac muscle cell differentiation / myofibroblast differentiation / connective tissue replacement involved in inflammatory response wound healing / odontoblast differentiation / negative regulation of macrophage cytokine production / positive regulation of receptor signaling pathway via STAT / TGFBR2 Kinase Domain Mutants in Cancer / positive regulation of isotype switching to IgA isotypes / positive regulation of mesenchymal stem cell proliferation / membrane protein intracellular domain proteolysis / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / heart valve morphogenesis / positive regulation of vasculature development / hyaluronan catabolic process / regulation of transforming growth factor beta receptor signaling pathway / ATP biosynthetic process / receptor catabolic process / negative regulation of extracellular matrix disassembly / positive regulation of extracellular matrix assembly / type II transforming growth factor beta receptor binding / TGFBR1 LBD Mutants in Cancer / positive regulation of chemotaxis / negative regulation of biomineral tissue development / type I transforming growth factor beta receptor binding / cell-cell junction organization / negative regulation of myoblast differentiation / positive regulation of vascular permeability / deubiquitinase activator activity / transforming growth factor beta binding / response to cholesterol / positive regulation of endothelial cell apoptotic process / microglia development / positive regulation of chemokine (C-X-C motif) ligand 2 production / aortic valve morphogenesis / positive regulation of fibroblast migration / phosphate-containing compound metabolic process / negative regulation of protein localization to plasma membrane / sprouting angiogenesis / neural tube development / Molecules associated with elastic fibres / RUNX3 regulates CDKN1A transcription / positive regulation of epidermal growth factor receptor signaling pathway / ventricular cardiac muscle tissue morphogenesis / macrophage derived foam cell differentiation / negative regulation of fat cell differentiation / Syndecan interactions / superoxide metabolic process / negative regulation of cell-cell adhesion / positive regulation of interleukin-17 production / TGF-beta receptor signaling activates SMADs / negative regulation of cell differentiation / positive regulation of SMAD protein signal transduction / RUNX3 regulates p14-ARF / positive regulation of cell division / cellular response to low-density lipoprotein particle stimulus / negative regulation of blood vessel endothelial cell migration / negative regulation of cell cycle / ECM proteoglycans / positive regulation of vascular endothelial growth factor production / positive regulation of collagen biosynthetic process / epithelial to mesenchymal transition / positive regulation of epithelial to mesenchymal transition / positive regulation of blood vessel endothelial cell migration / vasculogenesis / lymph node development / chondrocyte differentiation / hematopoietic progenitor cell differentiation / salivary gland morphogenesis / extrinsic apoptotic signaling pathway / positive regulation of protein dephosphorylation / regulation of cell migration / cellular response to transforming growth factor beta stimulus / antigen binding / positive regulation of protein metabolic process / protein export from nucleus / Downregulation of TGF-beta receptor signaling / extracellular matrix / transforming growth factor beta receptor signaling pathway / positive regulation of superoxide anion generation / negative regulation of miRNA transcription / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / negative regulation of protein phosphorylation / platelet alpha granule lumen
Similarity search - Function
Transforming growth factor beta-1 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-1 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. / Leucine Rich repeat / Cystine-knot cytokine / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. / Leucine-rich repeat / Leucine-rich repeat domain superfamily
Similarity search - Domain/homology
Transforming growth factor beta-1 proprotein / Transforming growth factor beta activator LRRC33
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.01 Å
AuthorsDuan Z / Zhang Z
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32171201 China
CitationJournal: Nat Commun / Year: 2022
Title: Specificity of TGF-β1 signal designated by LRRC33 and integrin αβ.
Authors: Zelin Duan / Xuezhen Lin / Lixia Wang / Qiuxin Zhen / Yuefeng Jiang / Chuxin Chen / Jing Yang / Chia-Hsueh Lee / Yan Qin / Ying Li / Bo Zhao / Jianchuan Wang / Zhe Zhang /
Abstract: Myeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin αβ activates extracellular L-TGF-β1 to trigger ...Myeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin αβ activates extracellular L-TGF-β1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-β1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-β1/LRRC33 and integrin αβ/L-TGF-β1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-β1 but not the -β2 or -β3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin αβ and L-TGF-β1, which shows higher avidity and more efficient L-TGF-β1 activation than previously reported 1:2 binding mode. We also uncover that the disulfide-linked loop of the integrin subunit β determines its exquisite affinity to L-TGF-β1. Together, our findings provide important insights into the specificity of TGF-β1 signaling achieved by LRRC33 and integrin αβ.
History
DepositionJun 8, 2022-
Header (metadata) releaseAug 31, 2022-
Map releaseAug 31, 2022-
UpdateSep 7, 2022-
Current statusSep 7, 2022Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_33571.png

Downloads & links

-
Map

FileDownload / File: emd_33571.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.055 Å
Density
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-0.0017771141 - 1.8793257
Average (Standard dev.)0.0013395529 (±0.02495337)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 270.08 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_33571_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_33571_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : L-TGF-beta1 in complex with its anchor protein LRRC33

EntireName: L-TGF-beta1 in complex with its anchor protein LRRC33
Components
  • Complex: L-TGF-beta1 in complex with its anchor protein LRRC33
    • Protein or peptide: Transforming growth factor beta-1 proprotein
    • Protein or peptide: Transforming growth factor beta activator LRRC33
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

-
Supramolecule #1: L-TGF-beta1 in complex with its anchor protein LRRC33

SupramoleculeName: L-TGF-beta1 in complex with its anchor protein LRRC33 / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant cell: HEK293
Molecular weightTheoretical: 150 KDa

-
Macromolecule #1: Transforming growth factor beta-1 proprotein

MacromoleculeName: Transforming growth factor beta-1 proprotein / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.010402 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MPLLLLLPLL WAGALALSTC KTIDMELVKR KRIEAIRGQI LSKLRLASPP SQGEVPPGPL PEAVLALYNS TRDRVAGESA EPEPEPEAD YYAKEVTRVL MVETHNEIYD KFKQSTHSIY MFFNTSELRE AVPEPVLLSR AELRLLRLKL KVEQHVELYQ K YSNNSWRY ...String:
MPLLLLLPLL WAGALALSTC KTIDMELVKR KRIEAIRGQI LSKLRLASPP SQGEVPPGPL PEAVLALYNS TRDRVAGESA EPEPEPEAD YYAKEVTRVL MVETHNEIYD KFKQSTHSIY MFFNTSELRE AVPEPVLLSR AELRLLRLKL KVEQHVELYQ K YSNNSWRY LSNRLLAPSD SPEWLSFDVT GVVRQWLSRG GEIEGFRLSA HCSCDSRDNT LQVDINGFTT GRRGDLATIH GM NRPFLLL MATPLERAQH LQSSRHRRAL DTNYCFSSTE KNCCVRQLYI DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLD TQYSKV LALYNQHNPG ASAAPCCVPQ ALEPLPIVYY VGRKPKVEQL SNMIVRSCKC S

-
Macromolecule #2: Transforming growth factor beta activator LRRC33

MacromoleculeName: Transforming growth factor beta activator LRRC33 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 72.191219 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MPLLLLLPLL WAGALAWRNR SGTATAASQG VCKLVGGAAD CRGQSLASVP SSLPPHARML TLDANPLKTL WNHSLQPYPL LESLSLHSC HLERISRGAF QEQGHLRSLV LGDNCLSENY EETAAALHAL PGLRRLDLSG NALTEDMAAL MLQNLSSLRS V SLAGNTIM ...String:
MPLLLLLPLL WAGALAWRNR SGTATAASQG VCKLVGGAAD CRGQSLASVP SSLPPHARML TLDANPLKTL WNHSLQPYPL LESLSLHSC HLERISRGAF QEQGHLRSLV LGDNCLSENY EETAAALHAL PGLRRLDLSG NALTEDMAAL MLQNLSSLRS V SLAGNTIM RLDDSVFEGL ERLRELDLQR NYIFEIEGGA FDGLAELRHL NLAFNNLPCI VDFGLTRLRV LNVSYNVLEW FL ATGGEAA FELETLDLSH NQLLFFPLLP QYSKLRTLLL RDNNMGFYRD LYNTSSPREM VAQFLLVDGN VTNITTVSLW EEF SSSDLA DLRFLDMSQN QFQYLPDGFL RKMPSLSHLN LHQNCLMTLH IREHEPPGAL TELDLSHNQL SELHLAPGLA SCLG SLRLF NLSSNQLLGV PPGLFANARN ITTLDMSHNQ ISLCPLPAAS DRVGPPSCVD FRNMASLRSL SLEGCGLGAL PDCPF QGTS LTYLDLSSNW GVLNGSLAPL QDVAPMLQVL SLRNMGLHSS FMALDFSGFG NLRDLDLSGN CLTTFPRFGG SLALET LDL RRNSLTALPQ KAVSEQLSRG LRTIYLSQNP YDCCGVDGWG ALQHGQTVAD WAMVTCNLSS KIIRVTELPG GVPRDCK WE RLDLGSNSLE VLFQ

-
Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 1 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration3 mg/mL
BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.2 µm / Nominal defocus min: 0.8 µm
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.01 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 254673

-
Atomic model buiding 1

RefinementProtocol: OTHER
Output model

PDB-7y1r:
Human L-TGF-beta1 in complex with the anchor protein LRRC33

+
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