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Structure of a tetrameric MscL in an expanded intermediate state

机译：四聚体MscL处于扩展中间状态的结构

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The ability of cells to sense and respond to mechanical force underlies diverse processes such as touch and hearing in animals, gravitropism in plants, and bacterial osmoregulation. In bacteria, mechanosensation is mediated by the mechanosensitive channels of large (MscL), small (MscS), potassium-dependent (MscK) and mini (MscM) conductances. These channels act as 'emergency relief valves' protecting bacteria from lysis upon acute osmotic down-shock3. Among them, MscL has been intensively studied since the original identification and characterization 15 years ago. MscL is reversibly and directly gated by changes in membrane tension. In the open state, MscL forms a non-selective 3 nS conductance channel which gates at tensions close to the lytic limit of the bacterial membrane. An earlier crystal structure at 3.5 A resolution of a pentameric MscL from Mycobacterium tuberculosis represents a closed-state or non-conducting conformation. MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative non-conductive expanded state and at least three sub-conducting states. Although our understanding of the dosed and open states of MscL has been increasing, little is known about the structures of the intermediate states despite their importance in elucidating the complete gating process of MscL. Here we present the crystal structure of a carboxy-terminal truncation mutant (A95-120) of MscL from Staphylococcus aureus (SaMscL(CA26)) at 3.8 A resolution. Notably, SaMscL(CA26) forms a tetrameric channel with both transmembrane helices tilted away from the membrane normal at angles close to that inferred for the open state, probably corresponding to a non-conductive but partially expanded intermediate state.
机译：细胞感知和响应机械力的能力是多种过程的基础，例如动物的触摸和听觉，植物的引力作用和细菌渗透调节。在细菌中，机械感应由大（MscL），小（MscS），钾依赖性（MscK）和小（MscM）电导的机械敏感通道介导。这些通道充当“紧急泄压阀”，可防止细菌在急性渗透下降时裂解。其中，自15年前最初的鉴定和表征以来，对MscL进行了深入研究。 MscL通过膜张力的变化可逆地直接控制。在打开状态下，MscL形成一个非选择性的3 nS电导通道，该通道以接近细菌膜溶解极限的张力进行门控。来自结核分枝杆菌的五聚体MscL的分辨率为3.5 A的较早晶体结构代表闭环或非导电构象。 MscL具有复杂的门控性能；它在闭合状态和打开状态之间表现出几种中间状态，包括一个假定的非导电扩展状态和至少三个子导电状态。尽管我们对MscL的剂量状态和打开状态的了解在不断增加，但是尽管它们对阐明MscL的完整门控过程很重要，但对中间状态的结构了解甚少。在这里，我们介绍了来自金黄色葡萄球菌（SaMscL（CA26））的MscL的羧基末端截短突变体（A95-120）的晶体结构，其分辨率为3.8A。值得注意的是，SaMscL（CA26）形成了一个四聚体通道，两个跨膜螺旋都以接近于打开状态推断的角度的角度倾斜，远离膜法线，可能对应于非导电但部分扩展的中间状态。

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  • 来源
    《Nature》 |2009年第7260期|120-124|共5页
  • 作者

    Zhenfeng Liu; Chris S. Gandhi; Douglas C. Rees;

  • 作者单位

    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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