Chemokine: receptor structure, interactions, and antagonism
Samantha J Allen1, Susan E Crown, Tracy M Handel
1Skaggs School of Pharmacy and Pharmaceutical Science, University of California, San Diego, La Jolla, California 92093, USA. samallen@ucsd.edu
Annual Review of Immunology
|February 13, 2007
Summary
Chemokines mediate cell migration but can cause diseases like HIV, inflammation, and cancer when dysregulated. Understanding chemokine:receptor interactions is key to developing new drugs for these conditions.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Chemokines are essential for immune cell trafficking and function.
- Dysregulation of chemokine signaling pathways is implicated in various diseases, including viral infections, inflammatory conditions, and cancer.
- Chemokine receptors, G protein-coupled receptors, are crucial for mediating these cellular responses.
Purpose of the Study:
- To review the current understanding of chemokine:receptor structure and function.
- To highlight the role of chemokine:receptor interactions in disease pathogenesis.
- To discuss the implications for drug discovery, particularly the development of receptor antagonists.
Main Methods:
- Review of existing literature on chemokine and chemokine receptor structure and function.
- Analysis of mutagenesis studies and structural data of ligands and mutant receptors.
- Integration of findings related to small molecule binding to identify key receptor residues.
Main Results:
- Chemokine binding to receptors induces conformational changes and downstream signaling.
- Structural insights from ligand-receptor interactions and mutagenesis studies reveal antagonism mechanisms.
- Identification of critical residues within receptor-binding pockets through small molecule binding studies.
Conclusions:
- Chemokine:receptor interactions are fundamental to immune cell dynamics and disease development.
- Targeting chemokine receptors offers a promising therapeutic strategy for diseases driven by aberrant chemokine signaling.
- Further structural and functional studies are crucial for advancing chemokine-based drug discovery.
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