[English] 日本語
Yorodumi
- PDB-6mxt: Crystal structure of human beta2 adrenergic receptor bound to sal... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6mxt
TitleCrystal structure of human beta2 adrenergic receptor bound to salmeterol and Nb71
Components
  • Endolysin, Beta-2 adrenergic receptor chimera
  • nanobody Nb71
KeywordsSIGNALING PROTEIN/HORMONE / G protein-coupled receptor / adrenergic receptor / asthma drug / active conformation / nanobody / SIGNALING PROTEIN-HORMONE complex / membrane protein
Function / homology
Function and homology information


beta2-adrenergic receptor activity / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / positive regulation of AMPA receptor activity / norepinephrine binding / positive regulation of autophagosome maturation / heat generation / Adrenoceptors / activation of transmembrane receptor protein tyrosine kinase activity ...beta2-adrenergic receptor activity / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / positive regulation of AMPA receptor activity / norepinephrine binding / positive regulation of autophagosome maturation / heat generation / Adrenoceptors / activation of transmembrane receptor protein tyrosine kinase activity / negative regulation of smooth muscle contraction / positive regulation of lipophagy / negative regulation of multicellular organism growth / negative regulation of G protein-coupled receptor signaling pathway / response to psychosocial stress / endosome to lysosome transport / adrenergic receptor signaling pathway / diet induced thermogenesis / positive regulation of protein kinase A signaling / neuronal dense core vesicle / adenylate cyclase binding / smooth muscle contraction / bone resorption / potassium channel regulator activity / positive regulation of bone mineralization / brown fat cell differentiation / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of sodium ion transport / viral release from host cell by cytolysis / response to cold / peptidoglycan catabolic process / receptor-mediated endocytosis / clathrin-coated endocytic vesicle membrane / positive regulation of protein serine/threonine kinase activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / cellular response to amyloid-beta / cell wall macromolecule catabolic process / Cargo recognition for clathrin-mediated endocytosis / lysozyme / lysozyme activity / positive regulation of cold-induced thermogenesis / Clathrin-mediated endocytosis / amyloid-beta binding / G alpha (s) signalling events / host cell cytoplasm / transcription by RNA polymerase II / positive regulation of MAPK cascade / lysosome / early endosome / receptor complex / cell surface receptor signaling pathway / endosome membrane / Ub-specific processing proteases / endosome / defense response to bacterium / apical plasma membrane / protein-containing complex binding / Golgi apparatus / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / identical protein binding / membrane / nucleus / plasma membrane
Similarity search - Function
Beta 2 adrenoceptor / Adrenoceptor family / Endolysin T4 type / T4-type lysozyme / : / Glycoside hydrolase, family 24 / Phage lysozyme / Lysozyme domain superfamily / Serpentine type 7TM GPCR chemoreceptor Srsx / G-protein coupled receptors family 1 signature. ...Beta 2 adrenoceptor / Adrenoceptor family / Endolysin T4 type / T4-type lysozyme / : / Glycoside hydrolase, family 24 / Phage lysozyme / Lysozyme domain superfamily / Serpentine type 7TM GPCR chemoreceptor Srsx / 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) / Lysozyme-like domain superfamily
Similarity search - Domain/homology
HEPTANE-1,2,3-TRIOL / salmeterol / NICKEL (II) ION / OLEIC ACID / (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / Endolysin / Endolysin / Beta-2 adrenergic receptor
Similarity search - Component
Biological speciesEnterobacteria phage T4 (virus)
Homo sapiens (human)
Lama glama (llama)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.95934213525 Å
AuthorsMasureel, M. / Zou, Y. / Picard, L.P. / van der Westhuizen, E. / Mahoney, J.P. / Rodrigues, J.P.G.L.M. / Mildorf, T.J. / Dror, R.O. / Shaw, D.E. / Bouvier, M. ...Masureel, M. / Zou, Y. / Picard, L.P. / van der Westhuizen, E. / Mahoney, J.P. / Rodrigues, J.P.G.L.M. / Mildorf, T.J. / Dror, R.O. / Shaw, D.E. / Bouvier, M. / Pardon, E. / Steyaert, J. / Sunahara, R.K. / Weis, W.I. / Zhang, C. / Kobilka, B.K.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)5U19GM106990-05 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)1R35GM128641-01 United States
CitationJournal: Nat. Chem. Biol. / Year: 2018
Title: Structural insights into binding specificity, efficacy and bias of a beta2AR partial agonist.
Authors: Masureel, M. / Zou, Y. / Picard, L.P. / van der Westhuizen, E. / Mahoney, J.P. / Rodrigues, J.P.G.L.M. / Mildorf, T.J. / Dror, R.O. / Shaw, D.E. / Bouvier, M. / Pardon, E. / Steyaert, J. / ...Authors: Masureel, M. / Zou, Y. / Picard, L.P. / van der Westhuizen, E. / Mahoney, J.P. / Rodrigues, J.P.G.L.M. / Mildorf, T.J. / Dror, R.O. / Shaw, D.E. / Bouvier, M. / Pardon, E. / Steyaert, J. / Sunahara, R.K. / Weis, W.I. / Zhang, C. / Kobilka, B.K.
History
DepositionOct 31, 2018Deposition site: RCSB / Processing site: RCSB
SupersessionNov 14, 2018ID: 6CSY
Revision 1.0Nov 14, 2018Provider: repository / Type: Initial release
Revision 1.1Jan 1, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_conn_type
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr1_symmetry / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.ptnr3_symmetry / _pdbx_struct_conn_angle.value / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr1_symmetry / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry / _struct_conn_type.id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Endolysin, Beta-2 adrenergic receptor chimera
N: nanobody Nb71
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,73111
Polymers67,0022
Non-polymers1,7309
Water36020
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4820 Å2
ΔGint-36 kcal/mol
Surface area26780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)178.682, 52.589, 125.917
Angle α, β, γ (deg.)90.0, 123.859, 90.0
Int Tables number5
Space group name H-MC121
Space group name HallC2y
Symmetry operation#1: x,y,z
#2: -x,y,-z
#3: x+1/2,y+1/2,z
#4: -x+1/2,y+1/2,-z

-
Components

-
Protein / Antibody , 2 types, 2 molecules AN

#1: Protein Endolysin, Beta-2 adrenergic receptor chimera / Lysis protein / Lysozyme / Muramidase / Beta-2 adrenoreceptor / Beta-2 adrenoceptor


Mass: 53528.066 Da / Num. of mol.: 1
Fragment: chimera of T4 lysozyme fused to human beta2 adrenergic receptor (UNP residues 29-234,263-365)
Mutation: M96T, M98T, N187E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Enterobacteria phage T4 (virus), (gene. exp.) Homo sapiens (human)
Gene: e, T4Tp126, ADRB2, ADRB2R, B2AR / Plasmid: pVL1392 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: D9IEF7, UniProt: P07550, UniProt: P00720*PLUS, lysozyme
#2: Antibody nanobody Nb71


Mass: 13473.763 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli)

-
Non-polymers , 8 types, 29 molecules

#3: Chemical ChemComp-K5Y / salmeterol / 2-(hydroxymethyl)-4-[(1R)-1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl]phenol


Mass: 415.566 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H37NO4 / Feature type: SUBJECT OF INVESTIGATION / Comment: agonist*YM
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-NI / NICKEL (II) ION


Mass: 58.693 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Ni
#6: Chemical ChemComp-OLC / (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / 1-Oleoyl-R-glycerol


Mass: 356.540 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H40O4
#7: Chemical ChemComp-HTO / HEPTANE-1,2,3-TRIOL


Mass: 148.200 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C7H16O3
#8: Chemical ChemComp-OLA / OLEIC ACID


Mass: 282.461 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H34O2
#9: Chemical ChemComp-P33 / 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL / HEPTAETHYLENE GLYCOL / PEG330


Mass: 326.383 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H30O8 / Comment: precipitant*YM
#10: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 20 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.8 Å3/Da / Density % sol: 67.64 %
Crystal growTemperature: 293.15 K / Method: lipidic cubic phase / pH: 7.5
Details: 31-34% PEG400, 100 mM HEPES, pH 7.5, 1% 1,2,3-heptanetriol

-
Data collection

DiffractionMean temperature: 77 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 0.987 Å
DetectorType: MAR CCD 130 mm / Detector: CCD / Date: Dec 18, 2012
RadiationMonochromator: Double crystal cryo-cooled Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.987 Å / Relative weight: 1
ReflectionResolution: 2.95→30 Å / Num. obs: 18742 / % possible obs: 92.6 % / Redundancy: 3.3 % / Biso Wilson estimate: 52.7347764892 Å2 / Rmerge(I) obs: 0.167 / Net I/σ(I): 1.52
Reflection shellResolution: 2.95→3.09 Å / Rmerge(I) obs: 0.525 / Mean I/σ(I) obs: 1.52 / Num. unique obs: 1012 / Χ2: 7.5 / % possible all: 75

-
Processing

Software
NameVersionClassification
HKL-20001.9_1692data collection
PHENIX1.9_1692refinement
PHASERphasing
Cootmodel building
SCALEPACKdata scaling
HKL-2000data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entries 4GBR & 4LDE

4gbr

4lde


Resolution: 2.95934213525→28.5196106168 Å / SU ML: 0.402084390742 / Cross valid method: FREE R-VALUE / σ(F): 1.38231122584 / Phase error: 24.3772282005
RfactorNum. reflection% reflection
Rfree0.24486451981 1135 6.05591719133 %
Rwork0.204625198648 --
obs0.207099158562 18742 90.7558955983 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 53.7137652891 Å2
Refinement stepCycle: LAST / Resolution: 2.95934213525→28.5196106168 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4539 0 111 20 4670
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.001949980790854768
X-RAY DIFFRACTIONf_angle_d0.5707627610766443
X-RAY DIFFRACTIONf_chiral_restr0.0213092559887723
X-RAY DIFFRACTIONf_plane_restr0.00270009590516797
X-RAY DIFFRACTIONf_dihedral_angle_d11.72955989381731
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.9593-3.09390.3385902513671070.2952837919271554X-RAY DIFFRACTION65.0607128868
3.0939-3.25680.3026209288811340.2799352545432127X-RAY DIFFRACTION89.085894405
3.2568-3.46050.3171605210181450.2579550973322234X-RAY DIFFRACTION93.0387172468
3.4605-3.72710.2520696961931490.2221268483532320X-RAY DIFFRACTION95.6976744186
3.7271-4.10120.2563665686691460.1997028631182327X-RAY DIFFRACTION96.2256809339
4.1012-4.69240.2115281182551500.1776583891152341X-RAY DIFFRACTION96.6252909232
4.6924-5.90330.2165169884771520.1824608738052347X-RAY DIFFRACTION96.2634822804
5.9033-28.52090.2082526205241520.1692108568852357X-RAY DIFFRACTION93.6543486376

+
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