Chemokine receptor 5 (CCR5) (CCR5)

Chemokine receptor 5 (CCR5) is a G protein-coupled receptor predominantly expressed on the surface of white blood cells, particularly T cells, macrophages, and dendritic cells. Structurally, it belongs to the class A GPCR family, characterized by seven transmembrane helices connected by extracellular and intracellular loops, with critical disulfide bonds stabilizing its extracellular architecture[1][3]. CCR5 binds chemokines such as CCL3 (MIP-1α), CCL4 (MIP-1β), and CCL5 (RANTES), mediating immune cell migration and inflammatory responses[1]. It serves as a major co-receptor for HIV-1 entry into host cells, making it a key target for anti-HIV therapeutics[1][3]. Individuals with a homozygous CCR5Δ32 mutation lack functional CCR5 and are resistant to HIV infection, but may have altered susceptibility to other infections[6]. Beyond HIV, CCR5 is implicated in the pathogenesis of inflammatory diseases, certain cancers, and autoimmune conditions, reflecting its broad role in immune regulation[4][8]. Drugs like Maraviroc inhibit CCR5 by stabilizing its inactive conformation, preventing HIV entry, and are being explored for applications in inflammation and oncology[3][4][8]. The receptor’s function is complex, with both protective and pathogenic roles depending on the disease context[6].

Other names

CC chemokine receptor type 5CCR-5CD195HIV-1 co-receptor

Allosteric inhibition (e.g., Maraviroc stabilizes inactive receptor conformation, blocking HIV-1 entry), Competitive inhibition (chemokine ligands block receptor engagement by HIV gp120), Modulation of leukocyte trafficking, Inhibition of signal transduction through G protein coupling