C-C chemokine receptor type 5 – Filamin A complex (CCR5-FLNA complex)

The C-C chemokine receptor type 5 – Filamin A complex (CCR5-FLNA complex) is a functional protein-protein assembly consisting of the G protein-coupled receptor CCR5 and the high-molecular-weight actin-binding protein Filamin A (Jimenez-Baranda et al., 2007). This complex is essential for the spatial organization of CCR5 on the plasma membrane and its coupling to the actin cytoskeleton, which facilitates efficient signal transduction and chemotaxis (Muñoz-Fernández et al., 2011). In the context of HIV-1 infection, the recruitment of Filamin A to the cytoplasmic tail of CCR5 is a critical requirement for viral fusion and entry into host CD4+ T cells (UniProt P51681). Beyond viral pathogenesis, the CCR5-FLNA interaction plays a significant role in cancer cell migration and metastasis, particularly in breast and prostate cancers where CCR5 is often overexpressed (Velasco-Velázquez et al., 2012). Therapeutic strategies targeting this complex primarily involve CCR5 antagonists like Maraviroc, which prevent the receptor from adopting the conformation necessary for FLNA recruitment and downstream signaling (PubMed ID: 17519368). Research into disrupting the specific protein-protein interface offers a potential avenue for inhibiting viral entry and tumor progression while minimizing off-target effects on other CCR5 functions.

Other names

CCR5 – FLNA-mediated complexCCR5-Filamin A interactionCCR5-FLNA signaling complexCCR5-Filamin A protein complex

Antagonism of the CCR5 receptor component to prevent ligand-induced conformational changes and the subsequent recruitment of Filamin A to the receptor's cytoplasmic tail, thereby inhibiting cytoskeletal rearrangements required for viral entry and cell migration (Jimenez-Baranda et al., 2007).