Evidence map›Paper›PMID 26302421›Full record

ArticleACS chemical biology2015

Engineering Metamorphic Chemokine Lymphotactin/XCL1 into the GAG-Binding, HIV-Inhibitory Dimer Conformation.

Jamie C Fox, Robert C Tyler, Christina Guzzo, Robbyn L Tuinstra, Francis C Peterson, Paolo Lusso, Brian F Volkman

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. The multifaceted role of XCL1 in health and disease.Protein science : a publication of the Protein Society · 2025
    Review
  2. Design and discovery of metamorphic proteins.Current opinion in structural biology · 2022
    Review
  3. Review
  4. Article
  5. Metamorphic Protein Folding Encodes Multiple Anti-Pathogens (Basel, Switzerland) · 2021
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Mechanisms of Regulation of the Chemokine-Receptor Network.International journal of molecular sciences · 2017
    Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. 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

7 authors at 3 institutions in 1 country.

Jamie C FoxDepartment of Biochemistry, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
Robert C TylerDepartment of Biochemistry, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
Christina GuzzoLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland 20892, United States.
Robbyn L TuinstraDepartment of Biochemistry, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
Francis C PetersonDepartment of Biochemistry, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
Paolo LussoLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland 20892, United States.
Brian F VolkmanDepartment of Biochemistry, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
Medical College of Wisconsin · USNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · US

Funding

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
Natural Antiviral Factors Expressed by CD8+T Cells and Other Immune System CellsZIAAI001041 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LUSSO, PAOLO · 2012 to 2017
$2.4M
Conformational duality in the human chemokine Ltn/XCL1R01AI063325 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI VOLKMAN, BRIAN F · 2005 to 2009
$1.4M
Intramural NIH HHS Z01 AI001041Intramural NIH HHS ZIA AI001041NIAID NIH HHS R01 AI058072NIAID NIH HHS R01 AI063325NIAID NIH HHS R37 AI058072PHS HHS AL05802PHS HHS AL103225
6 · The paper itself

Abstract

Unlike other chemokines, XCL1 undergoes a distinct metamorphic interconversion between a canonical monomeric chemokine fold and a unique β-sandwich dimer. The monomeric conformation binds and activates the receptor XCR1, whereas the dimer binds extracellular matrix glycosaminoglycans and has been associated with anti-human immunodeficiency virus (HIV) activity. Functional studies of WT-XCL1 are complex, as both conformations are populated in solution. To overcome this limitation, we engineered a stabilized dimeric variant of XCL1 designated CC5. This variant features a new disulfide bond (A36C-A49C) that prevents structural interconversion by locking the chemokine into the β-sandwich dimeric conformation, as demonstrated by NMR structural analysis and hydrogen/deuterium exchange experiments. Functional studies analyzing glycosaminoglycan binding demonstrate that CC5 binds with high affinity to heparin. In addition, CC5 exhibits potent inhibition of HIV-1 activity in primary peripheral blood mononuclear cells (PBMCs), demonstrating the importance of the dimer in blocking viral infection. Conformational variants like CC5 are valuable tools for elucidating the biological relevance of the XCL1 native-state interconversion and will assist in future antiviral and functional studies.

Indexed as

Anti-HIV AgentsChemokines, CDimerizationGenetic VariationGlycosaminoglycansHeparinHIV-1HIV InfectionsHumansLymphokinesProtein BindingProtein EngineeringSialoglycoproteinsStructure-Activity RelationshipAnti-HIV AgentsChemokines, CGlycosaminoglycansHeparinLymphokineslymphotactinSialoglycoproteinsXCL1 protein, human

Identifiers

PMID26302421
PMCPMC5028202
OpenAlexW1826357911

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.