Evidence map›Paper›PMID 30115951›Full record

ArticleScientific reports2018

Lysines and Arginines play non-redundant roles in mediating chemokine-glycosaminoglycan interactions.

Prem Raj B Joseph, Kirti V Sawant, Junji Iwahara, Roberto P Garofalo, Umesh R Desai, Krishna Rajarathnam

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. 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
1.4field-weighted citation impact, top 20% 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, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Transition Networks Unveil Disorder-to-Order Transformations in AInternational journal of molecular sciences · 2023
    Article
  9. Review
  10. Article
  11. Article
  12. NMR Methods for Characterization of Glycosaminoglycan-Chemokine Interactions.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  13. Review
  14. Regulation and functional roles of chemokines in liver diseases.Nature reviews. Gastroenterology & hepatology · 2021
    Review
  15. Article
  16. Review
  17. Article
  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

6 authors at 2 institutions in 1 country.

Prem Raj B JosephDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Kirti V SawantDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Junji IwaharaDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Roberto P GarofaloDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Umesh R DesaiDepartment of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.ORCID 0000-0002-1976-6597
Krishna RajarathnamDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA. krrajara@utmb.edu.
The University of Texas Medical Branch at Galveston · USVirginia Commonwealth University · US

Funding

Therapeutic assessment of synthetic heparin sulfates in transplantation modelsP01HL107152 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DESAI, UMESH RAMANLAL · 2011 to 2017
$15.8M
NHLBI NIH HHS P01 HL107152
6 · The paper itself

Abstract

Glycosaminoglycans (GAGs) bind a large array of proteins and mediate fundamental and diverse roles in human physiology. Ion pair interactions between protein lysines/arginines and GAG sulfates/carboxylates mediate binding. Neutrophil-activating chemokines (NAC) are GAG-binding proteins, and their sequences reveal high selectivity for lysines over arginines indicating they are functionally not equivalent. NAC binding to GAGs impacts gradient formation, receptor functions, and endothelial activation, which together regulate different components of neutrophil migration. We characterized the consequence of mutating lysine to arginine in NAC CXCL8, a well-characterized GAG-binding protein. We chose three lysines - two highly conserved lysines (K20 and K64) and a CXCL8-specific lysine (K67). Interestingly, the double K64R/K20R and K64R/K67R mutants are highly impaired in recruiting neutrophils in a mouse model. Further, both the mutants bind GAG heparin with higher affinity but show similar receptor activity. NMR and MD studies indicate that the structures are essentially identical to the WT, but the mutations alter the network of intramolecular ion pair interactions. These observations collectively indicate that the reduced in vivo recruitment is due to altered GAG interactions, higher GAG binding affinity can be detrimental, and specificity of lysines fine-tunes in vivo GAG interactions and function.

Indexed as

Amino Acid SequenceAnimalsArginineGlycosaminoglycansHeparinHydrogen BondingInterleukin-8LysineMiceMolecular Dynamics SimulationMutationNeutrophil InfiltrationProtein BindingSequence Homology, Amino AcidArginineGlycosaminoglycansHeparinInterleukin-8Lysine

Identifiers

PMID30115951
PMCPMC6095893
OpenAlexW2885853407

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.