Toshchakov Vladimir Y, Vogel Stefanie N
University of Maryland, Department of Microbiology and Immunology, School of Medicine, MD 21201-1559, Baltimore, USA.
Expert Opin Biol Ther. 2007 Jul;7(7):1035-50. doi: 10.1517/14712598.7.7.1035.
Toll-like receptors (TLR), a family of closely related type I, transmembrane, signal transducing proteins, sense invading pathogens early in the immune response to infection and deliver intracellular signals to the cell. Both TLRs and their adapter proteins possess a conserved region, the Toll/IL-1 resistance (TIR) domain. A subregion of approximately 14 amino acids within the TIR domain, the BB loop, enables interactions between certain TLRs or between certain TLRs and their adapter molecules. Use of cell-penetrating decoy peptides composed of the sequence of the Drosophila antennapedia peptide (16 amino acids) juxtaposed to a specific TIR BB loop 14 amino acid sequences enables an evaluation of the relative efficacy of such BB loop peptides to inhibit TIR-TIR interactions and signaling. Moreover, failure of specific BB loop peptides to inhibit signaling suggests that this region of a particular TIR domain is likely to not be involved in signaling. This review discusses cell-penetrating decoy peptides as a new tool to further understanding of the molecular interactions required for TLR signaling and evaluates the potential of this approach for the creation of therapeutic agents.
Toll样受体（TLR）是一类密切相关的I型跨膜信号转导蛋白家族，在对感染的免疫反应早期感知入侵病原体，并向细胞传递细胞内信号。TLR及其衔接蛋白都拥有一个保守区域，即Toll/IL-1抗性（TIR）结构域。TIR结构域内大约14个氨基酸的一个亚区域，即BB环，能够使某些TLR之间或某些TLR与其衔接分子之间发生相互作用。使用由果蝇触角足肽序列（16个氨基酸）与特定TIR BB环14个氨基酸序列并列组成的细胞穿透性诱饵肽，能够评估此类BB环肽抑制TIR-TIR相互作用和信号传导的相对效力。此外，特定BB环肽未能抑制信号传导表明特定TIR结构域的这一区域可能不参与信号传导。本综述讨论了细胞穿透性诱饵肽作为进一步了解TLR信号传导所需分子相互作用的新工具，并评估了这种方法用于创建治疗药物的潜力。
