Human Toll-Like Receptor 4 (hTLR4): Structural and functional dynamics in cancer

Abstract

Toll-Like Receptors (TLRs) recognize a wide variety of pathogen-associated molecular patterns and are centrally involved in the initiation of the innate and adaptive immune responses. Extensive analysis of TLRs has shown specificity in terms of ligand recognition, expression and cellular localization in different cell types and tissues, and most importantly, its role in the pathogenesis of multiple chronic inflammatory diseases. In recent past extensive investigations showed that many TLRs are profoundly expressed in various types of cancers. This review is emphasized on human TLR4 structural and functional dynamics in cancer. The review was intended to explore the present understanding of the involvement of hTLR4 in different types of cancer and different danger signals that can affect the expression and function of TLR4 in both normal and cancer cells. Dual role of TLR4 in cancer has also been discussed along with therapeutic targeting, cellular response via signaling and the possible conformational changes that occur in response to agonist and antagonist. This review provides a comprehensive resource for designing and discovery of novel TLR4 ligands for therapeutic intervention.

Keywords: PAMPs/DAMPs, protein-protein interaction; protein-ligand interaction; species specificity, computational drug discovery.