Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake

Thumbnail Image
Date
2022
Editors
Contact
Journal ISSN
Electronic ISSN
ISBN
Bibliographical data
Publisher
Series
DOI (citable link)
ArXiv-ID
International patent number
Link to the license
EU project number
Project
Open Access publication
Collections
Restricted until
Title in another language
Research Projects
Organizational Units
Journal Issue
Publication type
Journal article
Publication status
Published
Published in
Cells ; 11 (2022), 9. - 1444. - MDPI. - eISSN 2073-4409
Abstract
The chemokine receptor CCR7, together with its ligands, is responsible for the migration and positioning of adaptive immune cells, and hence critical for launching adaptive immune responses. CCR7 is also induced on certain cancer cells and contributes to metastasis formation. Thus, CCR7 expression and signalling must be tightly regulated for proper function. CCR7, like many other members of the G-protein coupled receptor superfamily, can form homodimers and oligomers. Notably, danger signals associated with pathogen encounter promote oligomerisation of CCR7 and is considered as one layer of regulating its function. Here, we assessed the dimerisation of human CCR7 and several single point mutations using split-luciferase complementation assays. We demonstrate that dimerisation-defective CCR7 mutants can be transported to the cell surface and elicit normal chemokine-driven G-protein activation. By contrast, we discovered that CCR7 mutants whose expression are shifted towards monomers significantly augment their capacities to bind and internalise fluorescently labelled CCL19. Modeling of the receptor suggests that dimerisation-defective CCR7 mutants render the extracellular loops more flexible and less structured, such that the chemokine recognition site located in the binding pocket might become more accessible to its ligand. Overall, we provide new insights into how the dimerisation state of CCR7 affects CCL19 binding and receptor trafficking.
Summary in another language
Subject (DDC)
570 Biosciences, Biology
Keywords
chemokine receptor CCR7; receptor dimerisation; receptor trafficking; chemokine binding; signalling; GPCR
Conference
Review
undefined / . - undefined, undefined. - (undefined; undefined)
Cite This
ISO 690GERKEN, Oliver J., Marc ARTINGER, Daniel LEGLER, 2022. Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake. In: Cells. MDPI. 11(9), 1444. eISSN 2073-4409. Available under: doi: 10.3390/cells11091444
BibTex
@article{Gerken2022-05Shift-57506,
  year={2022},
  doi={10.3390/cells11091444},
  title={Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake},
  number={9},
  volume={11},
  journal={Cells},
  author={Gerken, Oliver J. and Artinger, Marc and Legler, Daniel},
  note={Article Number: 1444}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/57506">
    <dc:creator>Gerken, Oliver J.</dc:creator>
    <dc:contributor>Gerken, Oliver J.</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-05-11T13:56:02Z</dcterms:available>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57506/1/Gerken_2-1maeykemb163o6.pdf"/>
    <dcterms:abstract xml:lang="eng">The chemokine receptor CCR7, together with its ligands, is responsible for the migration and positioning of adaptive immune cells, and hence critical for launching adaptive immune responses. CCR7 is also induced on certain cancer cells and contributes to metastasis formation. Thus, CCR7 expression and signalling must be tightly regulated for proper function. CCR7, like many other members of the G-protein coupled receptor superfamily, can form homodimers and oligomers. Notably, danger signals associated with pathogen encounter promote oligomerisation of CCR7 and is considered as one layer of regulating its function. Here, we assessed the dimerisation of human CCR7 and several single point mutations using split-luciferase complementation assays. We demonstrate that dimerisation-defective CCR7 mutants can be transported to the cell surface and elicit normal chemokine-driven G-protein activation. By contrast, we discovered that CCR7 mutants whose expression are shifted towards monomers significantly augment their capacities to bind and internalise fluorescently labelled CCL19. Modeling of the receptor suggests that dimerisation-defective CCR7 mutants render the extracellular loops more flexible and less structured, such that the chemokine recognition site located in the binding pocket might become more accessible to its ligand. Overall, we provide new insights into how the dimerisation state of CCR7 affects CCL19 binding and receptor trafficking.</dcterms:abstract>
    <dc:contributor>Artinger, Marc</dc:contributor>
    <dc:creator>Legler, Daniel</dc:creator>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57506/1/Gerken_2-1maeykemb163o6.pdf"/>
    <dc:contributor>Legler, Daniel</dc:contributor>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/57506"/>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dcterms:title>Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake</dcterms:title>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:issued>2022-05</dcterms:issued>
    <dc:language>eng</dc:language>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-05-11T13:56:02Z</dc:date>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Artinger, Marc</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
  </rdf:Description>
</rdf:RDF>
Internal note
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Contact
URL of original publication
Test date of URL
Examination date of dissertation
Method of financing
Comment on publication
Alliance license
Corresponding Authors der Uni Konstanz vorhanden
International Co-Authors
Bibliography of Konstanz
Yes
Refereed
Yes