Evidence map›Paper›PMID 27091995›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3.

Wenguang G Liang, Catherine G Triandafillou, Teng-Yi Huang, Medel Manuel L Zulueta, Shiladitya Banerjee, Aaron R Dinner, Shang-Cheng Hung, Wei-Jen Tang

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

49 citing papers in PubMed, 81 citations in OpenAlex.

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  11. Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023
    Review
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  18. The marriage of chemokines and galectins as functional heterodimers.Cellular and molecular life sciences : CMLS · 2021
    Review
  19. Article
  20. RHAMM Is a Multifunctional Protein That Regulates Cancer Progression.International journal of molecular sciences · 2021
    Review
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

8 authors at 2 institutions in 2 countries.

Wenguang G LiangBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637;
Catherine G TriandafillouGraduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL 60637;
Teng-Yi HuangGenomics Research Center, Academia Sinica, Taipei 115, Taiwan;
Medel Manuel L ZuluetaGenomics Research Center, Academia Sinica, Taipei 115, Taiwan;
Shiladitya BanerjeeJames Franck Institute, The University of Chicago, Chicago, IL 60637;
Aaron R DinnerJames Franck Institute, The University of Chicago, Chicago, IL 60637; Department of Chemistry, The University of Chicago, Chicago, IL 60637.
Shang-Cheng HungGenomics Research Center, Academia Sinica, Taipei 115, Taiwan; schung@gate.sinica.edu.tw wtang@uchicago.edu.
Wei-Jen TangBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637; schung@gate.sinica.edu.tw wtang@uchicago.edu.
University of Chicago · USGenomics Research Center, Academia Sinica · TW

Funding

Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Time resolved SAXS studies on the RP2/Arl3 complex pp.484-485P41GM103622 · NIGMS · ILLINOIS INSTITUTE OF TECHNOLOGY · PI IRVING, THOMAS C · 2012 to 2020
$11.9M
Graduate Program in Biophysical Sciences at the University of Chicago - Renewal 0T32EB009412 · NIBIB · UNIVERSITY OF CHICAGO · PI ENGEL, GREGORY S, SOSNICK, TOBIN R · 2009 to 2023
$4.9M
Regulation and Catalysis of Human Insulin Degrading EnzymeR01GM081539 · NIGMS · UNIVERSITY OF CHICAGO · PI TANG, WEI-JEN · 2007 to 2015
$2.6M
NCATS NIH HHS UL1 TR000430NIBIB NIH HHS T32 EB009412NIGMS NIH HHS P41 GM103622NIGMS NIH HHS R01 GM081539
6 · The paper itself

Abstract

CC chemokine ligand 5 (CCL5) and CCL3 are critical for immune surveillance and inflammation. Consequently, they are linked to the pathogenesis of many inflammatory conditions and are therapeutic targets. Oligomerization and glycosaminoglycan (GAG) binding of CCL5 and CCL3 are vital for the functions of these chemokines. Our structural and biophysical analyses of human CCL5 reveal that CCL5 oligomerization is a polymerization process in which CCL5 forms rod-shaped, double-helical oligomers. This CCL5 structure explains mutational data and offers a unified mechanism for CCL3, CCL4, and CCL5 assembly into high-molecular-weight, polydisperse oligomers. A conserved, positively charged BBXB motif is key for the binding of CC chemokines to GAG. However, this motif is partially buried when CCL3, CCL4, and CCL5 are oligomerized; thus, the mechanism by which GAG binds these chemokine oligomers has been elusive. Our structures of GAG-bound CCL5 and CCL3 oligomers reveal that these chemokine oligomers have distinct GAG-binding mechanisms. The CCL5 oligomer uses another positively charged and fully exposed motif, KKWVR, in GAG binding. However, residues from two partially buried BBXB motifs along with other residues combine to form a GAG-binding groove in the CCL3 oligomer. The N termini of CC chemokines are shown to be involved in receptor binding and oligomerization. We also report an alternative CCL3 oligomer structure that reveals how conformational changes in CCL3 N termini profoundly alter its surface properties and dimer-dimer interactions to affect GAG binding and oligomerization. Such complexity in oligomerization and GAG binding enables intricate, physiologically relevant regulation of CC chemokine functions.

Indexed as

Binding SitesChemokine CCL3Chemokine CCL5DimerizationGlycosaminoglycansHumansProtein BindingProtein ConformationStructure-Activity RelationshipCCL3 protein, humanCCL5 protein, humanChemokine CCL3Chemokine CCL5GlycosaminoglycansCC chemokineglycosaminoglycanprotein oligomerizationsignal transductionX-ray crystallography

Identifiers

PMID27091995
PMCPMC4983845
OpenAlexW2337411943

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.