Evidence map›Paper›PMID 28325822›Full record

ArticleScience signaling2017

Structural basis for chemokine recognition by a G protein-coupled receptor and implications for receptor activation.

Joshua J Ziarek, Andrew B Kleist, Nir London, Barak Raveh, Nicolas Montpas, Julien Bonneterre, Geneviève St-Onge, Crystal J DiCosmo-Ponticello, Chad A Koplinski, Ishan Roy and 10 more

Abstract read
In one paragraph

Article in Science signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
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  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Review
  15. Article
  16. Physiology of chemokines in the cancer microenvironment.American journal of physiology. Cell physiology · 2023
    Review
  17. Article
  18. The marriage of chemokines and galectins as functional heterodimers.Cellular and molecular life sciences : CMLS · 2021
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 9 institutions in 4 countries.

Joshua J ZiarekDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.ORCID http://orcid.org/0000-0002-3740-9999
Andrew B KleistDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.ORCID http://orcid.org/0000-0002-4954-010X
Nir LondonDepartment of Organic Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Barak RavehDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Nicolas MontpasCentre de Recherche, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Quebec H3T 1C5, Canada.ORCID http://orcid.org/0000-0003-4190-9424
Julien BonneterreCentre de Recherche, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Quebec H3T 1C5, Canada.
Geneviève St-OngeDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Quebec H3T 1J4, Canada.
Crystal J DiCosmo-PonticelloRutgers Graduate School of Biomedical Sciences, Newark, NJ 07101, USA.ORCID http://orcid.org/0000-0002-6213-6558
Chad A KoplinskiDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Ishan RoyDepartment of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Bryan StephensSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 93093, USA.
Sylvia ThelenInstitute for Research in Biomedicine, Università della Svizzera Italiana, Via Vela 6, Bellinzona CH-6500, Switzerland.
Christopher T VeldkampDepartment of Chemistry, University of Wisconsin-Whitewater, Whitewater, WI 53190, USA.
Frederick D CoffmanDepartment of Pathology and Laboratory Medicine and Center for Biophysical Pathology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
Marion C CohenRutgers Graduate School of Biomedical Sciences, Newark, NJ 07101, USA.ORCID http://orcid.org/0000-0002-4829-3709
Michael B DwinellDepartment of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Marcus ThelenInstitute for Research in Biomedicine, Università della Svizzera Italiana, Via Vela 6, Bellinzona CH-6500, Switzerland.
Francis C PetersonDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.ORCID http://orcid.org/0000-0001-9890-4224
Nikolaus HevekerCentre de Recherche, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Quebec H3T 1C5, Canada.
Brian F VolkmanDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA. bvolkman@mcw.edu.ORCID http://orcid.org/0000-0002-6681-5179
Medical College of Wisconsin · USCentre Hospitalier Universitaire Sainte-Justine · CARutgers, The State University of New Jersey · USUniversità della Svizzera italiana · CHUniversité de Montréal · CAUniversity of California, San Francisco · USUniversity of Montana · USUniversity of Wisconsin–Whitewater · USWeizmann Institute of Science · IL

Funding

Medical Scientist Training ProgramT32GM080202 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI BARBIERI, JOSEPH T, SALZMAN, NITA H · 2010 to 2024
$5.7M
Structural Basis for Chemokine FunctionR01AI058072 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI VOLKMAN, BRIAN F · 2004 to 2019
$4.1M
Structural Basis for Chemokine FunctionR37AI058072 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI Brian F Volkman · 2020 to 2026
$2.8M
Structural basis of chemokine receptor signaling in tumor progressionF30CA196040 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI KLEIST, ANDREW B · 2016 to 2020
$233k
NCI NIH HHS F30 CA196040NIAID NIH HHS R01 AI058072NIAID NIH HHS R37 AI058072NIGMS NIH HHS T32 GM080202
6 · The paper itself

Abstract

Chemokines orchestrate cell migration for development, immune surveillance, and disease by binding to cell surface heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The array of interactions between the nearly 50 chemokines and their 20 GPCR targets generates an extensive signaling network to which promiscuity and biased agonism add further complexity. The receptor CXCR4 recognizes both monomeric and dimeric forms of the chemokine CXCL12, which is a distinct example of ligand bias in the chemokine family. We demonstrated that a constitutively monomeric CXCL12 variant reproduced the G protein-dependent and β-arrestin-dependent responses that are associated with normal CXCR4 signaling and lead to cell migration. In addition, monomeric CXCL12 made specific contacts with CXCR4 that are not present in the structure of the receptor in complex with a dimeric form of CXCL12, a biased agonist that stimulates only G protein-dependent signaling. We produced an experimentally validated model of an agonist-bound chemokine receptor that merged a nuclear magnetic resonance-based structure of monomeric CXCL12 bound to the amino terminus of CXCR4 with a crystal structure of the transmembrane domains of CXCR4. The large CXCL12:CXCR4 protein-protein interface revealed by this structure identified previously uncharacterized functional interactions that fall outside of the classical "two-site model" for chemokine-receptor recognition. Our model suggests a mechanistic hypothesis for how interactions on the extracellular face of the receptor may stimulate the conformational changes required for chemokine receptor-mediated signal transduction.

Indexed as

Protein MultimerizationSignal TransductionAmino Acid Sequencebeta-Arrestin 2Cell Line, TumorCell MovementChemokine CXCL12HEK293 CellsHumansMagnetic Resonance SpectroscopyModels, MolecularMutationProtein BindingReceptors, CXCR4beta-Arrestin 2Chemokine CXCL12CXCR4 protein, humanReceptors, CXCR4

Identifiers

PMID28325822
PMCPMC5648539
OpenAlexW2600935377

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.