抗生素自问世以来,为疟疾、结核等传染性疾病的治疗做出了突出贡献,但是随着抗生素的滥用,耐药性细菌不断增多与细菌致病能力日益增强,导致有效的抗生素资源日益枯竭。因此,人类迫切需要寻找到抗菌新药或者抗生素的增效剂。大电导的机...抗生素自问世以来,为疟疾、结核等传染性疾病的治疗做出了突出贡献,但是随着抗生素的滥用,耐药性细菌不断增多与细菌致病能力日益增强,导致有效的抗生素资源日益枯竭。因此,人类迫切需要寻找到抗菌新药或者抗生素的增效剂。大电导的机械敏感通道(mechanosensitive channel of large conductance,MscL)是一类位于细菌细胞膜上的通道蛋白,直接感受膜张力的变化而开放,介导广泛的物质跨膜通透。MscL普遍存在于细菌,且不同MscL氨基酸序列具有很高的保守性,而在人和哺乳动物中没有MscL的同源体。目前,在新药研发中,MscL是热门的研究对象,对MscL与抗生素的相互作用及其潜在用途进行了综述。展开更多
大电导机械敏感性离子通道(Mechanosensitive channel of large conductance, MscL)是细菌上的一种机械敏感性离子通道,起到紧急释放阀门的作用,避免细菌在外界渗透压剧烈下降时破裂死亡。MscL开放口径大,易于修饰、突变和表达,重构于...大电导机械敏感性离子通道(Mechanosensitive channel of large conductance, MscL)是细菌上的一种机械敏感性离子通道,起到紧急释放阀门的作用,避免细菌在外界渗透压剧烈下降时破裂死亡。MscL开放口径大,易于修饰、突变和表达,重构于脂质体上仍有活性,是生物纳米技术领域良好的工具分子。近年来MscL在生物纳米技术领域的应用已有大量成果,研究发现通过修饰、突变后的MscL蛋白可以作为纳米给药系统上的分子开关,具有通透孔径和电荷的选择性,并受到光、pH及磁场等环境因素调控。对MscL在生物纳米技术领域的应用研究进行综述。展开更多
Mechanosensitive（MS） ion channels play an important role in various physiological processes.Although the determination of the structure of mechanosensitive channel of large conductance（MscL） makes the simulation s...Mechanosensitive（MS） ion channels play an important role in various physiological processes.Although the determination of the structure of mechanosensitive channel of large conductance（MscL） makes the simulation study possible,it has not so far been possible to directly simulate the gating mechanism of MscL in atomic detail.In this article,MscL has been studied via molecular dynamic（MD） simulations to gain a detailed description of the sensitivity to lateral tension and the gating pathway.MscL undergoes conformational rearrangement in sustaining lateral tension,and the open state is obtained when 2.0 MPa lateral tension is directly applied on the pure protein.During the opening process,Loop region responds to tension first,and the mechanical sensitivity is followed by S1 domain.Transmembrane（TM） bundle is the key position for channel opening,and the motion of TM1 helices finally realizes the significant expansion of the constricted gating pore.C-terminus domain presents expansion later during the TM opening.In our study,return of the whole protein to the initial closed state is achieved only in the early opening stage.During the relaxation from the open state,the TM helices are the most mobile domain,which is different from the opening process.展开更多
文摘抗生素自问世以来,为疟疾、结核等传染性疾病的治疗做出了突出贡献,但是随着抗生素的滥用,耐药性细菌不断增多与细菌致病能力日益增强,导致有效的抗生素资源日益枯竭。因此,人类迫切需要寻找到抗菌新药或者抗生素的增效剂。大电导的机械敏感通道(mechanosensitive channel of large conductance,MscL)是一类位于细菌细胞膜上的通道蛋白,直接感受膜张力的变化而开放,介导广泛的物质跨膜通透。MscL普遍存在于细菌,且不同MscL氨基酸序列具有很高的保守性,而在人和哺乳动物中没有MscL的同源体。目前,在新药研发中,MscL是热门的研究对象,对MscL与抗生素的相互作用及其潜在用途进行了综述。
文摘大电导机械敏感性离子通道(Mechanosensitive channel of large conductance, MscL)是细菌上的一种机械敏感性离子通道,起到紧急释放阀门的作用,避免细菌在外界渗透压剧烈下降时破裂死亡。MscL开放口径大,易于修饰、突变和表达,重构于脂质体上仍有活性,是生物纳米技术领域良好的工具分子。近年来MscL在生物纳米技术领域的应用已有大量成果,研究发现通过修饰、突变后的MscL蛋白可以作为纳米给药系统上的分子开关,具有通透孔径和电荷的选择性,并受到光、pH及磁场等环境因素调控。对MscL在生物纳米技术领域的应用研究进行综述。
基金supported by the National Basic Research Program of China (973 Program) (2012CB518502)the National Natural Science Foundation of China (81102630)+2 种基金the Shanghai Leading Academic Discipline Project (S30304,B112)the Science Foundation of Shanghai Municipal Commission of Science and Technology (09DZ1976600,09dZ1974303,10DZ1975800)the Fudan Science Foundation for Young (09FQ07)
文摘Mechanosensitive（MS） ion channels play an important role in various physiological processes.Although the determination of the structure of mechanosensitive channel of large conductance（MscL） makes the simulation study possible,it has not so far been possible to directly simulate the gating mechanism of MscL in atomic detail.In this article,MscL has been studied via molecular dynamic（MD） simulations to gain a detailed description of the sensitivity to lateral tension and the gating pathway.MscL undergoes conformational rearrangement in sustaining lateral tension,and the open state is obtained when 2.0 MPa lateral tension is directly applied on the pure protein.During the opening process,Loop region responds to tension first,and the mechanical sensitivity is followed by S1 domain.Transmembrane（TM） bundle is the key position for channel opening,and the motion of TM1 helices finally realizes the significant expansion of the constricted gating pore.C-terminus domain presents expansion later during the TM opening.In our study,return of the whole protein to the initial closed state is achieved only in the early opening stage.During the relaxation from the open state,the TM helices are the most mobile domain,which is different from the opening process.
