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Life with Bacterial Mechanosensitive Channels, from Discovery to Physiology to Pharmacological Target.
Microbiology and Molecular Biology Reviews ( IF 12.9 ) Pub Date : 2020-01-15 , DOI: 10.1128/mmbr.00055-19
Paul Blount 1 , Irene Iscla 1
Affiliation  

General principles in biology have often been elucidated from the study of bacteria. This is true for the bacterial mechanosensitive channel of large conductance, MscL, the channel highlighted in this review. This channel functions as a last-ditch emergency release valve discharging cytoplasmic solutes upon decreases in osmotic environment. Opening the largest gated pore, MscL passes molecules up to 30 Å in diameter; exaggerated conformational changes yield advantages for study, including in vivo assays. MscL contains structural/functional themes that recur in higher organisms and help elucidate how other, structurally more complex, channels function. These features of MscL include (i) the ability to directly sense, and respond to, biophysical changes in the membrane, (ii) an α helix ("slide helix") or series of charges ("knot in a rope") at the cytoplasmic membrane boundary to guide transmembrane movements, and (iii) important subunit interfaces that, when disrupted, appear to cause the channel to gate inappropriately. MscL may also have medical applications: the modality of the MscL channel can be changed, suggesting its use as a triggered nanovalve in nanodevices, including those for drug targeting. In addition, recent studies have shown that the antibiotic streptomycin opens MscL and uses it as one of the primary paths to the cytoplasm. Moreover, the recent identification and study of novel specific agonist compounds demonstrate that the channel is a valid drug target. Such compounds may serve as novel-acting antibiotics and adjuvants, a way of permeabilizing the bacterial cell membrane and, thus, increasing the potency of commonly used antibiotics.

中文翻译:

从发现到生理再到药理学目标的细菌机械敏感通道的生活。

生物学的一般原理经常从细菌的研究中得到阐明。对于大电导的细菌机械敏感通道MscL(在本评论中突出显示的通道),这是正确的。该通道用作最后一道紧急释放阀,可在渗透环境降低时释放细胞质溶质。MscL打开最大的门控孔,使直径可达30Å的分子通过;夸大的构象变化产生了包括体内试验在内的研究优势。MscL包含在高等生物中反复出现的结构/功能主题,并有助于阐明其他结构更复杂的通道如何发挥作用。MscL的这些特征包括(i)直接感知并响应膜中生物物理变化的能力,(ii)α螺旋(“ slide helix”)或一系列电荷(“
更新日期:2020-01-15
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