[English] 日本語
Yorodumi
- EMDB-45982: Structure of SH3 domain of Src in complex with beta-arrestin 1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-45982
TitleStructure of SH3 domain of Src in complex with beta-arrestin 1
Map data
Sample
  • Complex: Beta-arrestin 1 bound to a G protein-coupled receptor phosphopeptide and antibody fragment Fab30 in complex with SH3 domain of Src
    • Protein or peptide: Antibody fragment Fab30, heavy chain
    • Protein or peptide: Antibody fragment Fab30, light chain
    • Protein or peptide: Vasopressin V2 receptor
    • Protein or peptide: Beta-arrestin-1
    • Protein or peptide: Proto-oncogene tyrosine-protein kinase Src
KeywordsGPCR signaling / arrestin / Src / SH3 / SIGNALING PROTEIN
Function / homology
Function and homology information


V2 vasopressin receptor binding / regulation of inositol trisphosphate biosynthetic process / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / TGFBR3 regulates TGF-beta signaling / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / sensory perception of touch / G alpha (s) signalling events / Vasopressin-like receptors ...V2 vasopressin receptor binding / regulation of inositol trisphosphate biosynthetic process / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / TGFBR3 regulates TGF-beta signaling / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / sensory perception of touch / G alpha (s) signalling events / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / alpha-1B adrenergic receptor binding / follicle-stimulating hormone signaling pathway / protein phosphorylated amino acid binding / Lysosome Vesicle Biogenesis / angiotensin receptor binding / Golgi Associated Vesicle Biogenesis / AP-2 adaptor complex binding / Ub-specific processing proteases / MAP2K and MAPK activation / hemostasis / Signaling by ERBB2 / Nuclear signaling by ERBB4 / Signaling by SCF-KIT / Regulation of KIT signaling / Signaling by EGFR / GAB1 signalosome / Regulation of gap junction activity / FCGR activation / PECAM1 interactions / Co-stimulation by CD28 / Co-inhibition by CTLA4 / EPHA-mediated growth cone collapse / Ephrin signaling / G alpha (i) signalling events / GP1b-IX-V activation signalling / Thrombin signalling through proteinase activated receptors (PARs) / VEGFR2 mediated cell proliferation / RET signaling / Receptor Mediated Mitophagy / ADP signalling through P2Y purinoceptor 1 / RAF activation / PIP3 activates AKT signaling / EPH-ephrin mediated repulsion of cells / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Activated NTRK3 signals through PI3K / Downstream signal transduction / Downregulation of ERBB4 signaling / Cyclin D associated events in G1 / Regulation of RUNX3 expression and activity / telencephalon development / MAP2K and MAPK activation / Cargo recognition for clathrin-mediated endocytosis / Integrin signaling / GRB2:SOS provides linkage to MAPK signaling for Integrins / DCC mediated attractive signaling / MET activates PTK2 signaling / Extra-nuclear estrogen signaling / clathrin adaptor activity / EPHB-mediated forward signaling / p130Cas linkage to MAPK signaling for integrins / VEGFA-VEGFR2 Pathway / negative regulation of interleukin-8 production / Clathrin-mediated endocytosis / regulation of G protein-coupled receptor signaling pathway / connexin binding / G protein-coupled receptor internalization / arrestin family protein binding / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / Thrombin signalling through proteinase activated receptors (PARs) / response to morphine / mitogen-activated protein kinase kinase binding / clathrin binding / positive regulation of Rho protein signal transduction / stress fiber assembly / negative regulation of intrinsic apoptotic signaling pathway / positive regulation of systemic arterial blood pressure / pseudopodium / negative regulation of interleukin-6 production / positive regulation of intracellular signal transduction / positive regulation of insulin secretion involved in cellular response to glucose stimulus / positive regulation of receptor internalization / endocytic vesicle / immune system process / negative regulation of Notch signaling pathway / phototransduction / progesterone receptor signaling pathway / cellular response to hormone stimulus / activation of adenylate cyclase activity / clathrin-coated pit / insulin-like growth factor receptor binding / positive regulation of vasoconstriction / negative regulation of protein ubiquitination / response to cytokine / GTPase activator activity / positive regulation of protein ubiquitination / nuclear estrogen receptor binding / negative regulation of extrinsic apoptotic signaling pathway / non-membrane spanning protein tyrosine kinase activity
Similarity search - Function
Vasopressin V2 receptor / Vasopressin receptor / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain / Arrestin (or S-antigen), N-terminal domain / Arrestin (or S-antigen), C-terminal domain ...Vasopressin V2 receptor / Vasopressin receptor / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain / Arrestin (or S-antigen), N-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin-like, C-terminal / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Src homology 3 domains / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Immunoglobulin E-set / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Proto-oncogene tyrosine-protein kinase Src / Beta-arrestin-1 / Vasopressin V2 receptor
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat) / Mus musculus (house mouse) / Homo sapiens (human) / Gallus gallus (chicken)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.34 Å
AuthorsPakharukova N / Bansia H / Lefkowitz RJ / des Georges A
Funding support United States, European Union, France, 5 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL016037-50 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM133598 United States
European Molecular Biology Organization (EMBO)ALTF 1071-2017European Union
Human Frontier Science Program (HFSP)LT000174/2018 France
CitationJournal: bioRxiv / Year: 2024
Title: Beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy.
Authors: Natalia Pakharukova / Brittany N Thomas / Harsh Bansia / Linus Li / Rinat R Abzalimov / Jihee Kim / Alem W Kahsai / Biswaranjan Pani / Dana K Bassford / Shibo Liu / Xingdong Zhang / Amedee ...Authors: Natalia Pakharukova / Brittany N Thomas / Harsh Bansia / Linus Li / Rinat R Abzalimov / Jihee Kim / Alem W Kahsai / Biswaranjan Pani / Dana K Bassford / Shibo Liu / Xingdong Zhang / Amedee des Georges / Robert J Lefkowitz /
Abstract: Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we use ...Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we use cryo-electron microscopy to elucidate how βarr1 recruits and activates non-receptor tyrosine kinase Src. βarr1 binds Src SH3 domain via two distinct sites: a polyproline site in the N-domain and a non-proline site in the central crest region. At both sites βarr1 interacts with the aromatic surface of SH3 which is critical for Src autoinhibition, suggesting that βarr1 activates Src by SH3 domain displacement. Binding of SH3 to the central crest region induces structural rearrangements in the β-strand V, finger, and middle loops of βarr1 and interferes with βarr1 coupling to the receptor core potentially impacting receptor desensitization and downstream signaling.
History
DepositionJul 31, 2024-
Header (metadata) releaseNov 13, 2024-
Map releaseNov 13, 2024-
UpdateNov 27, 2024-
Current statusNov 27, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_45982.png

Downloads & links

-
Map

FileDownload / File: emd_45982.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.38 Å/pix.
x 300 pix.
= 414.72 Å		1.38 Å/pix.
x 300 pix.
= 414.72 Å		1.38 Å/pix.
x 300 pix.
= 414.72 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.3824 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.45
Minimum - Maximum-2.5270495 - 4.380165
Average (Standard dev.)0.00092025695 (±0.033950083)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 414.72 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_45982_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_45982_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Beta-arrestin 1 bound to a G protein-coupled receptor phosphopept...

EntireName: Beta-arrestin 1 bound to a G protein-coupled receptor phosphopeptide and antibody fragment Fab30 in complex with SH3 domain of Src
Components
  • Complex: Beta-arrestin 1 bound to a G protein-coupled receptor phosphopeptide and antibody fragment Fab30 in complex with SH3 domain of Src
    • Protein or peptide: Antibody fragment Fab30, heavy chain
    • Protein or peptide: Antibody fragment Fab30, light chain
    • Protein or peptide: Vasopressin V2 receptor
    • Protein or peptide: Beta-arrestin-1
    • Protein or peptide: Proto-oncogene tyrosine-protein kinase Src

-
Supramolecule #1: Beta-arrestin 1 bound to a G protein-coupled receptor phosphopept...

SupramoleculeName: Beta-arrestin 1 bound to a G protein-coupled receptor phosphopeptide and antibody fragment Fab30 in complex with SH3 domain of Src
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Rattus norvegicus (Norway rat)

-
Macromolecule #1: Antibody fragment Fab30, heavy chain

MacromoleculeName: Antibody fragment Fab30, heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 25.512354 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String:
EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDK THHHHHHHH

-
Macromolecule #2: Antibody fragment Fab30, light chain

MacromoleculeName: Antibody fragment Fab30, light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.435064 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String:
SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC

-
Macromolecule #3: Vasopressin V2 receptor

MacromoleculeName: Vasopressin V2 receptor / type: protein_or_peptide / ID: 3
Details: Synthetic phosphopeptide mimicking the C-tail of vasopressin 2 receptor
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 3.550936 KDa
SequenceString:
ARGR(TPO)PP(SEP)LG PQDE(SEP)C(TPO)(TPO)A(SEP) (SEP)(SEP)LAKDTSS

UniProtKB: Vasopressin V2 receptor

-
Macromolecule #4: Beta-arrestin-1

MacromoleculeName: Beta-arrestin-1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 44.04916 KDa
Recombinant expressionOrganism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
SequenceString: GDKGTRVFKK ASPNGKLTVY LGKRDFVDHI DLVDPVDGVV LVDPEYLKER RVYVTLTVAF RYGREDLDVL GLTFRKDLFV ANVQSFPPA PCDKKPLTRL QERLIKKLGE HAYPFTFEIP PNLPSSVTLQ PGPEDTGKAL GVDYEVKAFV AENLEEKIHK R NSVRLVIR ...String:
GDKGTRVFKK ASPNGKLTVY LGKRDFVDHI DLVDPVDGVV LVDPEYLKER RVYVTLTVAF RYGREDLDVL GLTFRKDLFV ANVQSFPPA PCDKKPLTRL QERLIKKLGE HAYPFTFEIP PNLPSSVTLQ PGPEDTGKAL GVDYEVKAFV AENLEEKIHK R NSVRLVIR KVQYAPERPG PQPTAETTRQ FLMSDKPLHL EASLDKEIYY HGEPISVNVH VTNNTNKTVK KIKISVRQYA DI VLFNTAQ YKVPVAMEEA DDTVAPSSTF SKVYTLTPFL ANNREKRGLA LDGKLKHEDT NLASSTLLRE GANREILGII VSY KVKVKL VVSRGGLLGD LASSDVAVEL PFTLMHPKPK EEPPHREVPE SETPVDTNLI ELDTNDDDIV FEDFAR

UniProtKB: Beta-arrestin-1

-
Macromolecule #5: Proto-oncogene tyrosine-protein kinase Src

MacromoleculeName: Proto-oncogene tyrosine-protein kinase Src / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO / EC number: non-specific protein-tyrosine kinase
Source (natural)Organism: Gallus gallus (chicken)
Molecular weightTheoretical: 9.756567 KDa
Recombinant expressionOrganism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
SequenceString:
MGSSHHHHHH DYDIPTTENL YFQGHMVTTF VALYDYESCT ETDLSFKKGE RLQIVNNTEG DWWLAHSLTT GQTGYIPSNY VAPSD

UniProtKB: Proto-oncogene tyrosine-protein kinase Src

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration8 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 53.8 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

4jqi

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.34 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.1.0) / Number images used: 345529
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial model
PDB IDChain

4jqi

source_name: PDB, initial_model_type: experimental model

4jqi

chain_id: V, source_name: PDB, initial_model_type: experimental model

4jqi

chain_id: L, source_name: PDB, initial_model_type: experimental model

4jqi

chain_id: H, source_name: PDB, initial_model_type: experimental model

2ptk

chain_id: B, source_name: PDB, initial_model_type: experimental model
Output model

PDB-9cx9:
Structure of SH3 domain of Src in complex with beta-arrestin 1

+
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