The role of protein-protein interactions in Toll-like receptor function.

摘要: As part of the innate immune system, Toll-like receptors (TLRs) represent key players in first line defense against invading foreign pathogens, and are also major targets for therapeutic immunomodulation. TLRs type I transmembrane proteins composed an ectodomain responsible ligand binding, a single-pass domain, cytoplasmic Toll/Interleukin-1 receptor (TIR) signaling domain. The ectodomains specialized recognizing wide variety pathogen-associated molecular patterns, ranging from lipids lipopeptides to nucleic acid fragments. members TLR family highly conserved their characteristic, solenoidal leucine-rich repeats (LRRs). Upon these rigid LRR scaffolds dimerize (or re-organize case pre-formed dimers) bring together carboxy-terminal TIR domains. latter proposed act as platform recruitment adaptor formation higher-order complexes, resulting propagation downstream cascades. In this review, we discuss protein-protein interactions critical stability productive, ligand-bound complexes. particular, focus on large body high-resolution crystallographic data now available homo- heterodimeric well inhibitory TLR-like receptors, consider computational approaches that can facilitate our understanding ligand-induced conformational changes associated with function. We briefly what is known about involved both domain assembly TIR-mediated complex light recent structural biochemical data.