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- PDB-7o7f: Structural basis of the activation of the CC chemokine receptor 5... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7o7f | |||||||||||||||
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Title | Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist | |||||||||||||||
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Function / homology | ![]() regulation of chronic inflammatory response / CCR4 chemokine receptor binding / chemokine receptor antagonist activity / activation of phospholipase D activity / chemokine (C-C motif) ligand 5 binding / positive regulation of cellular biosynthetic process / CCR1 chemokine receptor binding / positive regulation of natural killer cell chemotaxis / negative regulation of macrophage apoptotic process / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | ![]() ![]() ![]() | |||||||||||||||
![]() | Isaikina, P. / Tsai, C.-J. / Dietz, N.B. / Pamula, F. / Goldie, K.N. / Schertler, G.F.X. / Maier, T. / Stahlberg, H. / Deupi, X. / Grzesiek, S. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist. Authors: Polina Isaikina / Ching-Ju Tsai / Nikolaus Dietz / Filip Pamula / Anne Grahl / Kenneth N Goldie / Ramon Guixà-González / Camila Branco / Marianne Paolini-Bertrand / Nicolas Calo / Fabrice ...Authors: Polina Isaikina / Ching-Ju Tsai / Nikolaus Dietz / Filip Pamula / Anne Grahl / Kenneth N Goldie / Ramon Guixà-González / Camila Branco / Marianne Paolini-Bertrand / Nicolas Calo / Fabrice Cerini / Gebhard F X Schertler / Oliver Hartley / Henning Stahlberg / Timm Maier / Xavier Deupi / Stephan Grzesiek / ![]() ![]() Abstract: The human CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) that plays a major role in inflammation and is involved in cancer, HIV, and COVID-19. Despite its importance as a drug ...The human CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) that plays a major role in inflammation and is involved in cancer, HIV, and COVID-19. Despite its importance as a drug target, the molecular activation mechanism of CCR5, i.e., how chemokine agonists transduce the activation signal through the receptor, is yet unknown. Here, we report the cryo-EM structure of wild-type CCR5 in an active conformation bound to the chemokine super-agonist [6P4]CCL5 and the heterotrimeric G protein. The structure provides the rationale for the sequence-activity relation of agonist and antagonist chemokines. The N terminus of agonist chemokines pushes onto specific structural motifs at the bottom of the orthosteric pocket that activate the canonical GPCR microswitch network. This activation mechanism differs substantially from other CC chemokine receptors that bind chemokines with shorter N termini in a shallow binding mode involving unique sequence signatures and a specialized activation mechanism. | |||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 259.4 KB | Display | ![]() |
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PDB format | ![]() | 209.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 12746MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 40415.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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#2: Protein | Mass: 37416.930 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#4: Protein | Mass: 8556.918 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: UNP P02698 / Source: (natural) ![]() ![]() ![]() |
-Protein , 2 types, 2 molecules CI
#3: Protein | Mass: 42726.168 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: UNP P51681 / Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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#5: Protein | ![]() Mass: 7857.123 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: UNP P13501 / Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
-Antibody , 2 types, 2 molecules HF
#6: Antibody | Mass: 23542.248 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
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#7: Antibody | Mass: 23921.592 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
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Molecular weight | Units: KILODALTONS/NANOMETER / Experimental value: NO | ||||||||||||||||||||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 2.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||||||||||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 49 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2466 |
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Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: NONE | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.15 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 345458 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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Atomic model building |
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Refine LS restraints |
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