Activation of chemokine receptors

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Rohou A, Grigorieff N. Zivanov, J. Elife 7 , Quantifying the local resolution of cryo-EM density maps. Pettersen EF, et al. UCSF Chimera—a visualization system for exploratory research and analysis. Comput Chem. T cells that encounter antigen in mesenteric lymph nodes draining the small intestine will often express CCR9 to enable homing back to the small intestine , , , This depends on the specialization of DC and stromal cells in the mesenteric lymph nodes and production of retinoic acid from dietary vitamin A , , , , , The chemokine network is enormously complex, comprising of a large number of interacting ligands, receptors, and regulatory proteins engaged in overlapping and diverse cellular processes.

The induction of migration, particularly of leukocytes, is its central biological purpose, but its influence extends far beyond this. The physiological contribution of the chemokine network is substantial, with fundamental roles in development, homeostasis, immune surveillance, inflammation, protection from infection, tissue repair, and innate and adaptive immunity. Virtually all diseases involve chemokines and their receptors in some way, some more prominently than others, and although clinical translation has been slow, drugs targeting cCKRs have successfully made it to clinic.

The first chemokine was discovered over 40 years ago, and our understanding of the chemokines and their receptors is now well advanced. Nonetheless, there is still much to uncover, and chemokines and their receptors are likely to remain prominent in the scientific literature for years to come. Both authors planned the article structure and content.

RJBN wrote the text and constructed the Figures. CH reviewed and edited the article, and helped with literature search and referencing. National Center for Biotechnology Information , U. The Febs Journal. FEBS J. Published online Apr Catherine E. Hughes 1 and Robert J. Nibbs 1. Robert J. Author information Article notes Copyright and License information Disclaimer.

Nibbs, Email: ku. Corresponding author. This article has been cited by other articles in PMC. Keywords: atypical chemokine receptor, cell migration, chemokine, chemokine receptor, glycosaminoglycan, immune surveillance, inflammation, leukocyte, oligomerization, protease.

Chemokines Chemokines are defined by their primary amino acid sequence and the arrangement of specific structurally important cysteine residues within the mature protein. Open in a separate window. Figure 1. Chemokine receptors There are two families of heptahelical surface molecules that bind to chemokines: conventional chemokine receptors cCKRs and atypical chemokine receptors ACKRs Fig. Atypical chemokine receptors Atypical chemokine receptors, of which there are four yellow boxes, Fig.

The function of the chemokine network By far the most studied function of the chemokine network is cell migration, particularly of leukocytes. Figure 2. Figure 3.

Figure 4. Infection, inflammation, and immunopathology Chemokines, along with an array of other proteins, peptides, lipids, and microbial products, direct leukocyte recruitment into infected or damaged tissues 66 , Chemokine receptor switching Changes in leukocyte function are intimately associated with switches in cCKR expression.

Concluding remarks The chemokine network is enormously complex, comprising of a large number of interacting ligands, receptors, and regulatory proteins engaged in overlapping and diverse cellular processes.

Author contributions Both authors planned the article structure and content. References 1. Int J Mol Sci 18 , Genes Cells 18 , 1— Science , — Eur J Immunol 32 , — J Immunol , — Immunol Lett , 15— Semin Immunol 18 , — Nomenclature for chemokine receptors. Pharmacol Rev 52 , — Immunity 12 , — Nat Immunol 12 , — J Biol Chem , — Nature , — Nat Immunol 1 , — Blood , — Gene , — Cell Mol Immunol 14 , 1— Sci Signal 9 , ra J Leukoc Biol 99 , — Exp Cell Res , — Curr Biol 22 , — Immunity 41 , — Annu Rev Biochem 74 , — Immunity 33 , — Br J Pharmacol , — Sci Transl Med 9 , eaai Glycobiology 26 , — Nat Med 15 , 97— Sci Transl Med 9 , eaah J Exp Med , — Sci Rep 7 , Oncotarget 7 , — Front Immunol 7 , J Autoimmun 85 , 45— J Leukoc Biol 82 , — Immunity 32 , — Cell , — Nat Immunol 16 , — Cell 96 , — Structure 22 , — Mol Cell Biol 26 , — Biochem Pharmacol , 53— Recently, a small subset of chemokine receptors, now identified as "atypical chemokine receptors" ACKRs , has been described.

These receptors lack classic GPCR signaling and chemotactic activity and are believed to limit inflammation through their ability to scavenge chemokines at the inflammatory sites. Recent studies have highlighted a role for ACKRs in neuroinflammation. Title: Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor. Abstract Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors GPCRs.

Authors: Burg, John S. Burg, John S. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor. United States: N. Copy to clipboard. United States. Free Publicly Available Full Text.

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