【摘 要】
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Background: Profilin is involved in motility and invasion of apicomplexan (protozoan) parasites and is used for invading host cells.In 2005, mouse Toll-like receptor (TLR) 11 was found to initiate an
【机 构】
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Cancer Research Center, School of Medicine, Shandong University, Jinan 250012, China
【出 处】
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第五届全国生物信息学与系统生物学学术大会
论文部分内容阅读
Background: Profilin is involved in motility and invasion of apicomplexan (protozoan) parasites and is used for invading host cells.In 2005, mouse Toll-like receptor (TLR) 11 was found to initiate an innate immune response inducing interleukin-12 (IL-12) upon sensing Toxoplasma gondii profilins.However, the molecular mechanism of TLRll binding profilins remains unknown.On the other hand, the TLRll expression is suppressed in humans.Thus, whether other TLRs can recognize parasite profilins in human instead of TLR11 becomes a mystery.Methods: We first analyzed the structural features of the crystal structure of T.gondii profilin (PDB code: 3NEC) and a homology model of mouse TLR11.Then, protein-protein docking and molecular dynamics simulation (MDS) methods were used to generate a TLR11-profilin complex model.Finally, a similarity search of the potential profilin-binding site based on structure features was performed across all human TLR models (TLR1-10).Results: Electrostatic analysis reveals that the entire surface of the T.gondii profilin is predominantly negatively charged, whereas TLR11 exhibits several positively charged patches.Docking and MDS studies provided a model of TLR11-profilin complex structure.The model shows that the potential profilin-binding site is a positively charged patch located at LRR1 to LRR7 on TLR11, which is rich in Ser, Thr, Cys and lactam amino acids.Very interestingly, a similar structure pattern just appeared on human TLR* (exact TLR family number hidden due to unpublished data).Accordingly, we proposed a potential model of human TLR* interacting with profilin.Conclusions: The profilin-binding site of mouse TLR11 processes a specified structural pattern.We suggest that human TLR* that also has this pattern might recognize parasite profilin.If it is true, it will enlighten new therapeutic measures for human infectious diseases .
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