Medical College of Wisconsin
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Modeling the complete chemokine-receptor interaction. Methods Cell Biol 2019;149:289-314

Date

01/09/2019

Pubmed ID

30616825

Pubmed Central ID

PMC6790067

DOI

10.1016/bs.mcb.2018.09.005

Scopus ID

2-s2.0-85055739819   1 Citation

Abstract

Chemokines are soluble, secreted proteins that induce chemotaxis of leukocytes and other cells. Migratory cells can sense the chemokine concentration gradient following chemokine binding and activation of chemokine receptors, a subset of the G protein-coupled receptor (GPCR) superfamily. Chemokine receptor signaling plays a central role in cell migration during inflammatory responses as well as in cancer and other diseases. Given their important role in mediating essential pathologic and physiologic processes, chemokines and their receptors are attractive targets for therapeutic development. A better understanding of the molecular basis of chemokine-GPCR interactions will aid in the understanding of the mechanistic basis for chemokine function in disease-related processes, as well as aid in the design of new therapeutics. High resolution protein structures are critical for determining these mechanisms and investigating the interactions between approximately 50 chemokines and 20 chemokine receptors. Currently, three unique structures of chemokine-GPCR complexes have been determined and have greatly broadened our knowledge of this large protein-protein interaction. While these structures represent only a small fraction of clinically relevant chemokines and receptors, they can be exploited as scaffolds for homology modeling to understand the chemokine-GPCR interactions. This chapter presents a specialized methodology to construct and validate models of chemokine-GPCR complexes using the Rosetta software suite.

Author List

Wedemeyer MJ, Mueller BK, Bender BJ, Meiler J, Volkman BF

Author

Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Humans
Models, Molecular
Receptors, Chemokine
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