Hydrophobic mismatch between the hydrophobic length of membrane proteins and hydrophobic thickness of membranes is a crucial factor in controlling protein function and assembly.We combined fluorescence with circular d...Hydrophobic mismatch between the hydrophobic length of membrane proteins and hydrophobic thickness of membranes is a crucial factor in controlling protein function and assembly.We combined fluorescence with circular dichroism（CD） and attenuated total reflection infrared（ATR-IR） spectroscopic methods to investigate the behaviors of the peptide and lipids under hydrophobic mismatch using a model peptide from the fourth transmembrane domain of natural resistance-associated macrophage protein 1（Nramp1）,the phosphatidylcholines（PCs） and phosphatidylglycerols（PGs） with different lengths of acyl chains（14：0,16：0 and 18：0）.In all PG lipid membranes,the peptide forms stable α-helix structure,and the helix axis is parallel to lipid chains.The helical span and orientation hardly change in varying thickness of PG membranes,while the lipid chains can deform to accommodate to the hydrophobic surface of embedded peptide.By comparison,the helical structures of the model peptide in PC lipid membranes are less stable.Upon incorporation with PC lipid membranes,the peptide can deform itself to accommodate to the hydrophobic thickness of lipid membranes in response to hydrophobic mismatch.In addition,hydrophobic mismatch can increase the aggregation propensity of the peptide in both PC and PG lipid membranes and the peptide in PC membranes has more aggregation tendency than that in PG membranes.展开更多
Delivery of therapeutic peptides or proteins into tissues is severely limited by the size and biochemical properties of the molecules. Protein transduction domain (PTD)-mediated cargo transduction represents a novel a...Delivery of therapeutic peptides or proteins into tissues is severely limited by the size and biochemical properties of the molecules. Protein transduction domain (PTD)-mediated cargo transduction represents a novel and promising strategy to deliver biologically active peptides in vivo. The first PTD was identified from the HIV-1 transactivating transcriptional activator protein Tat in 1988. Since then, other PTDs have also been identified, including the third α-helix of the antennapedia homeotic transcription factor and synthetic peptide carriers. However, Tat PTD (amino acids 47 - 57) has shown markedly better ability for intracellular delivery than other PTDs. It has been demonstrated that fusion peptides containing the Tat PTD enter the central nervous system after systemic administration. Our previous study has shown that i.p. injected Tat-PSD-95 PDZ2 expresses in the central nervous system and significantly disrupts PDZ domain-mediated protein interactions between PSD-95 and N-methyl-D-aspartate receptor subunit NR2A/2B, thereby alleviating chronic pain. Therefore, Tat-mediated intracellular delivery can be used for systemic administration of analgesics in pain management.展开更多
In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed t...In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat cysteine rich peptide increase CCR5 expression in human monocytes, and this activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5 expression in monocytes. These results provide insight into a new mechanism by which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.展开更多
蛋白质Tat转运系统不同于细菌中普遍存在的Sec转运系统 ,而与植物叶绿体中蛋白质转运的ΔpH依赖系统相似 .通过Tat系统转运的蛋白质底物含有特征性的双精氨酸保守序列核心S/T R R x F L K的信号肽 ,其h区的疏水性低 ,c区有由高赖氨酸、...蛋白质Tat转运系统不同于细菌中普遍存在的Sec转运系统 ,而与植物叶绿体中蛋白质转运的ΔpH依赖系统相似 .通过Tat系统转运的蛋白质底物含有特征性的双精氨酸保守序列核心S/T R R x F L K的信号肽 ,其h区的疏水性低 ,c区有由高赖氨酸、高精氨酸构成的避开Sec系统信号 ,信号肽和成熟蛋白质的组成对蛋白质的转运都有影响 .TatA、TatB、TatC和TatE四种蛋白质参与了大肠杆菌的Tat转运系统 .被转运的底物蛋白质绝大多数为与细菌厌氧呼吸有关的含氧化还原辅因子的酶 ,并以折叠形式转运 .展开更多
基金Supported by the National Natural Science Foundation of China(Nos.20973083,20934002)
文摘Hydrophobic mismatch between the hydrophobic length of membrane proteins and hydrophobic thickness of membranes is a crucial factor in controlling protein function and assembly.We combined fluorescence with circular dichroism（CD） and attenuated total reflection infrared（ATR-IR） spectroscopic methods to investigate the behaviors of the peptide and lipids under hydrophobic mismatch using a model peptide from the fourth transmembrane domain of natural resistance-associated macrophage protein 1（Nramp1）,the phosphatidylcholines（PCs） and phosphatidylglycerols（PGs） with different lengths of acyl chains（14：0,16：0 and 18：0）.In all PG lipid membranes,the peptide forms stable α-helix structure,and the helix axis is parallel to lipid chains.The helical span and orientation hardly change in varying thickness of PG membranes,while the lipid chains can deform to accommodate to the hydrophobic surface of embedded peptide.By comparison,the helical structures of the model peptide in PC lipid membranes are less stable.Upon incorporation with PC lipid membranes,the peptide can deform itself to accommodate to the hydrophobic thickness of lipid membranes in response to hydrophobic mismatch.In addition,hydrophobic mismatch can increase the aggregation propensity of the peptide in both PC and PG lipid membranes and the peptide in PC membranes has more aggregation tendency than that in PG membranes.
文摘Delivery of therapeutic peptides or proteins into tissues is severely limited by the size and biochemical properties of the molecules. Protein transduction domain (PTD)-mediated cargo transduction represents a novel and promising strategy to deliver biologically active peptides in vivo. The first PTD was identified from the HIV-1 transactivating transcriptional activator protein Tat in 1988. Since then, other PTDs have also been identified, including the third α-helix of the antennapedia homeotic transcription factor and synthetic peptide carriers. However, Tat PTD (amino acids 47 - 57) has shown markedly better ability for intracellular delivery than other PTDs. It has been demonstrated that fusion peptides containing the Tat PTD enter the central nervous system after systemic administration. Our previous study has shown that i.p. injected Tat-PSD-95 PDZ2 expresses in the central nervous system and significantly disrupts PDZ domain-mediated protein interactions between PSD-95 and N-methyl-D-aspartate receptor subunit NR2A/2B, thereby alleviating chronic pain. Therefore, Tat-mediated intracellular delivery can be used for systemic administration of analgesics in pain management.
文摘In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat cysteine rich peptide increase CCR5 expression in human monocytes, and this activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5 expression in monocytes. These results provide insight into a new mechanism by which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.
文摘蛋白质Tat转运系统不同于细菌中普遍存在的Sec转运系统 ,而与植物叶绿体中蛋白质转运的ΔpH依赖系统相似 .通过Tat系统转运的蛋白质底物含有特征性的双精氨酸保守序列核心S/T R R x F L K的信号肽 ,其h区的疏水性低 ,c区有由高赖氨酸、高精氨酸构成的避开Sec系统信号 ,信号肽和成熟蛋白质的组成对蛋白质的转运都有影响 .TatA、TatB、TatC和TatE四种蛋白质参与了大肠杆菌的Tat转运系统 .被转运的底物蛋白质绝大多数为与细菌厌氧呼吸有关的含氧化还原辅因子的酶 ,并以折叠形式转运 .
