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Chemokines and galectins form heterodimers to modulate inflammation
- Source :
- Embo Reports, 21(4):47852. Wiley, EMBO reports, EMBO Reports
- Publication Year :
- 2020
-
Abstract
- Chemokines and galectins are simultaneously upregulated and mediate leukocyte recruitment during inflammation. Until now, these effector molecules have been considered to function independently. Here, we tested the hypothesis that they form molecular hybrids. By systematically screening chemokines for their ability to bind galectin‐1 and galectin‐3, we identified several interacting pairs, such as CXCL12 and galectin‐3. Based on NMR and MD studies of the CXCL12/galectin‐3 heterodimer, we identified contact sites between CXCL12 β‐strand 1 and Gal‐3 F‐face residues. Mutagenesis of galectin‐3 residues involved in heterodimer formation resulted in reduced binding to CXCL12, enabling testing of functional activity comparatively. Galectin‐3, but not its mutants, inhibited CXCL12‐induced chemotaxis of leukocytes and their recruitment into the mouse peritoneum. Moreover, galectin‐3 attenuated CXCL12‐stimulated signaling via its receptor CXCR4 in a ternary complex with the chemokine and receptor, consistent with our structural model. This first report of heterodimerization between chemokines and galectins reveals a new type of interaction between inflammatory mediators that can underlie a novel immunoregulatory mechanism in inflammation. Thus, further exploration of the chemokine/galectin interactome is warranted.<br />Chemokines and galectins are simultaneously upregulated during inflammation and mediate leukocyte recruitment. A systematic screen now demonstrates their physical interaction as heterodimers, identifying several novel interacting pairs.
- Subjects :
- Chemokine
DIMERIZATION
G protein‐coupled receptor
Biochemistry
Interactome
Mice
0302 clinical medicine
Structural Biology
BINDING
Leukocytes
chemotaxis
Receptor
NEUTROPHILS
0303 health sciences
biology
Chemistry
Effector
Articles
CXCL12
3. Good health
Cell biology
RECEPTORS
Galectin-3
Signal Transduction
animal structures
Galectins
Immunology
galectin‐3
Article
03 medical and health sciences
galectin-3
otorhinolaryngologic diseases
Genetics
Animals
TRAFFICKING
G protein-coupled receptor
MOLECULE
Molecular Biology
030304 developmental biology
Galectin
Inflammation
Chemotaxis
stomatognathic diseases
ATHEROSCLEROSIS
biology.protein
T-CELLS
PATTERNS
lectin
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 1469221X
- Database :
- OpenAIRE
- Journal :
- Embo Reports, 21(4):47852. Wiley, EMBO reports, EMBO Reports
- Accession number :
- edsair.doi.dedup.....57de8e91d01f6e0b4e33dcaf71611fe7