[English] 日本語
Yorodumi
- PDB-7f8x: Crystal structure of the cholecystokinin receptor CCKAR in comple... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7f8x
TitleCrystal structure of the cholecystokinin receptor CCKAR in complex with NN9056
Components
  • ASP-SMF-NLE-GLY-TRP-NLE-OEM-MEA-NH2 (NN9056)
  • Cholecystokinin receptor type A,Endolysin
KeywordsSTRUCTURAL PROTEIN / G protein-coulped receptor
Function / homology
Function and homology information


cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / peptide hormone binding / cellular response to hormone stimulus / viral release from host cell by cytolysis / forebrain development / peptidoglycan catabolic process / axonogenesis / Peptide ligand-binding receptors ...cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / peptide hormone binding / cellular response to hormone stimulus / viral release from host cell by cytolysis / forebrain development / peptidoglycan catabolic process / axonogenesis / Peptide ligand-binding receptors / neuron migration / cell wall macromolecule catabolic process / lysozyme / lysozyme activity / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / host cell cytoplasm / defense response to bacterium / G protein-coupled receptor signaling pathway / nucleoplasm / membrane / plasma membrane / cytosol
Similarity search - Function
Cholecystokinin receptor type A / Cholecystokinin A receptor, N-terminal / Cholecystokinin A receptor, N-terminal domain superfamily / Cholecystokinin A receptor, N-terminal / Cholecystokinin receptor / Endolysin T4 type / T4-type lysozyme / : / Glycoside hydrolase, family 24 / Phage lysozyme ...Cholecystokinin receptor type A / Cholecystokinin A receptor, N-terminal / Cholecystokinin A receptor, N-terminal domain superfamily / Cholecystokinin A receptor, N-terminal / Cholecystokinin receptor / 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. / Lysozyme-like domain superfamily / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family)
Similarity search - Domain/homology
Endolysin / Cholecystokinin receptor type A
Similarity search - Component
Biological speciesHomo sapiens (human)
Escherichia virus T4
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3 Å
AuthorsZhang, X. / He, C. / Wang, M. / Zhou, Q. / Yang, D. / Zhu, Y. / Wu, B. / Zhao, Q.
Funding support China, 10items
OrganizationGrant numberCountry
National Science Foundation (NSF, China)21704064 China
National Science Foundation (NSF, China)81773792 China
National Science Foundation (NSF, China)81973373 China
National Science Foundation (NSF, China)31800621 China
National Science Foundation (NSF, China)31770796 China
National Science Foundation (NSF, China)31971178 China
National Science Foundation (NSF, China)81872915 China
National Science Foundation (NSF, China)82073904 China
National Science Foundation (NSF, China)31825010 China
National Science Foundation (NSF, China)81525024 China
CitationJournal: Nat Chem Biol / Year: 2021
Title: Structures of the human cholecystokinin receptors bound to agonists and antagonists.
Authors: Xuefeng Zhang / Chenglin He / Mu Wang / Qingtong Zhou / Dehua Yang / Ya Zhu / Wenbo Feng / Hui Zhang / Antao Dai / Xiaojing Chu / Jia Wang / Zhenlin Yang / Yi Jiang / Ulrich Sensfuss / ...Authors: Xuefeng Zhang / Chenglin He / Mu Wang / Qingtong Zhou / Dehua Yang / Ya Zhu / Wenbo Feng / Hui Zhang / Antao Dai / Xiaojing Chu / Jia Wang / Zhenlin Yang / Yi Jiang / Ulrich Sensfuss / Qiuxiang Tan / Shuo Han / Steffen Reedtz-Runge / H Eric Xu / Suwen Zhao / Ming-Wei Wang / Beili Wu / Qiang Zhao /
Abstract: Cholecystokinin receptors, CCKR and CCKR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal ...Cholecystokinin receptors, CCKR and CCKR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal structures of the human CCKR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKR-gastrin in complex with G and G, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors.
History
DepositionJul 2, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 29, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: Data collection / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model / struct_conn
Item: _struct_conn.pdbx_leaving_atom_flag

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cholecystokinin receptor type A,Endolysin
C: ASP-SMF-NLE-GLY-TRP-NLE-OEM-MEA-NH2 (NN9056)


Theoretical massNumber of molelcules
Total (without water)61,5842
Polymers61,5842
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2020 Å2
ΔGint-9 kcal/mol
Surface area23360 Å2
MethodPISA
Unit cell
Length a, b, c (Å)56.600, 72.500, 87.000
Angle α, β, γ (deg.)90.00, 100.00, 90.00
Int Tables number4
Space group name H-MP1211
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

-
Components

#1: Protein Cholecystokinin receptor type A,Endolysin / CCK-A receptor / CCK-AR / Cholecystokinin-1 receptor / CCK1-R / Lysis protein / Lysozyme / Muramidase


Mass: 60451.352 Da / Num. of mol.: 1 / Mutation: F130W,C1251G,C1336A,C1293T,I1376R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Escherichia virus T4
Gene: CCKAR, CCKRA / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P32238, UniProt: P00720, lysozyme
#2: Protein/peptide ASP-SMF-NLE-GLY-TRP-NLE-OEM-MEA-NH2 (NN9056)


Mass: 1132.266 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.98 Å3/Da / Density % sol: 58.7 %
Crystal growTemperature: 293 K / Method: lipidic cubic phase
Details: 100 mM HEPES,7.5, 10 (v/v) PPG400 and 100 mM ammonium acetate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL41XU / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 28, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3→50 Å / Num. obs: 26470 / % possible obs: 97.1 % / Redundancy: 4.4 % / Biso Wilson estimate: 92.57 Å2 / Rmerge(I) obs: 0.206 / Net I/σ(I): 4.45
Reflection shellResolution: 3→3.08 Å / Rmerge(I) obs: 0.573 / Num. unique obs: 1376

-
Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
XDSVERSION Jan 26, 2018data reduction
XSCALEVERSION Jan 26, 2018data scaling
PHASER1.19.2phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5ZBQ

5zbq


Resolution: 3→29.54 Å / Cross valid method: FREE R-VALUE
Stereochemistry target values: GEOSTD + MONOMER LIBRARY + CDL V1.2
RfactorNum. reflection% reflection
Rfree0.261 2636 9.9 %
Rwork0.238 --
obs0.24 26392 97 %
Displacement parametersBiso mean: 117.8 Å2
Refinement stepCycle: LAST / Resolution: 3→29.54 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3597 0 0 0 3597
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0023674
X-RAY DIFFRACTIONf_angle_d0.6064986
X-RAY DIFFRACTIONf_dihedral_angle_d13.3991321
X-RAY DIFFRACTIONf_chiral_restr0.042583
X-RAY DIFFRACTIONf_plane_restr0.005610
LS refinement shellResolution: 3→3.107 Å /
RfactorNum. reflection
Rfree0.314 1374
Rwork0.382 -
Refinement TLS params.Method: refined / Origin x: 7.53177084276 Å / Origin y: -18.3595949578 Å / Origin z: 15.476184543 Å
111213212223313233
T1.10855393803 Å2-0.135518085941 Å2-0.0370280252725 Å2-0.620614901514 Å2-0.0390392845201 Å2--0.510489099751 Å2
L0.945987175415 °2-0.151727338934 °2-0.766421345947 °2-1.65077573876 °2-1.02175571854 °2--6.08095668291 °2
S-0.0987602121411 Å °-0.111233466821 Å °-0.0229849675833 Å °0.0441121862527 Å °-0.0391333933849 Å °-0.0463077007947 Å °-0.133198588253 Å °0.12848844065 Å °0.160157818729 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