Studies on recognition mechanism of oral microbes-derived lipopeptides by Toll-like receptors

toll样受体2 （TLR2）在微生物脂蛋白/脂肽的识别中起关键作用。然而，识别的分子机制细节仍不清楚。因此，本研究旨在确定TLR2识别微生物脂蛋白/脂肽的分子机制。我们发现了以下结果。细菌三酰化脂肽刺激巨噬细胞的活性水平低于支原体二酰化脂肽。支原体二酰化脂肽的脂质和肽部分都参与了TLR2.3的识别。107,112和115位亮氨酸残基参与了TLR2与TLR6.4联合识别支原体脂蛋白/脂肽和金黄色葡萄球菌肽聚糖的过程。在所有8个富含亮氨酸的TLR2重复序列中至少有一个亮氨酸残基，它与TLR6.5联合识别支原体脂蛋白/脂肽和金黄色葡萄球菌肽聚糖。富亮氨酸重复序列β-sheet结构中的亮氨酸残基参与了TLR2与TLR6.6联合识别支原体脂肽的过程。支原体脂蛋白具有通过TLR2/TLR2诱导HEK293细胞凋亡的活性，其活性由TLR2下游的FADD和MyD88介导。

Toll-like receptor 2 (TLR2)plays a key role in the recognition of microbial lipoproteins/lipoeppetides. However, details in molecular mechanisms of the recognition still remains unknown. This study was therefore carried out to determine the molecular mechanism by which TLR2 recognizes microbial lipoproteins/lipoeppetides.We have found the following findings.1.The level of the activity of bacterial triacylated lipopeptides to stimulate macrophages was lower than that of mycoplasmal diacylated lipoepptides.2.Both lipid and peptide portions of mycoplasmal diacylated lipopeptides are involved in the recognition by TLR2.3.Leucine residues at positions 107,112 and 115 are involved in the recognition of mycoplasmal lipoproteins/lipopeptide and S.aureus peptidoglycans by TLR2 in combination with TLR6.4.There is at least one leucine residue in all 8 leucine-rich repeats of TLR2 which is responsible for the the recognition of mycoplasmal lipoproteins/lipopeptide and S.aureus peptidoglycans by TLR2 in combination with TLR6.5.Leucine residues in β-sheet structure of leucine-rich repeats are involved in the recognition of mycoplasmal lipopeptides by TLR2 in combination with TLR6.6.Mycoplasmal lipoproteins possesses the activity to induce apoptosis of HEK293 cells through TLR2/TLR2 and the activity is mediated by FADD and MyD88 downstream of TLR2.