Structure of a tetrameric MscL in an expanded intermediate state.
Structure of a tetrameric MscL in an expanded intermediate state.
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作者：
细胞感知和响应机械力的能力是多种过程的基础，例如动物的触觉和听觉，植物的向重力性和细菌的呼吸调节。在细菌中，机械感觉由大（MscL）、小（MscS）、钾依赖性（MscK）和小（MscM）电导的机械敏感通道介导。这些通道作为“紧急减压阀”，保护细菌在急性渗透压下降时免于溶解。其中，MscL自15年前由Kung及其同事最初鉴定和表征以来一直被深入研究。MscL是可逆的，直接门控膜张力的变化。在开放状态下，MscL形成一个非选择性的3 ns-电导通道，其在接近细菌膜的裂解极限的张力下进行门控。来自结核分枝杆菌的五聚体MscL（TbMscL）在3.5 μ m分辨率下的早期晶体结构代表闭合状态或非导电构象。MscL具有复杂的门控行为;它在闭合状态和开放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。虽然我们对MscL的封闭态和开放态的理解不断增加，但对中间态的结构知之甚少，尽管它们在阐明MscL的完整门控过程中非常重要。在这里，我们提出了一个截断突变体（Δ95-120）的MscL从金黄色葡萄球菌（SaMscL-CΔ26）的晶体结构在3.8 nm分辨率。引人注目的是，SaMscL-CΔ26形成了一个四聚体通道，其中两个跨膜（TM）螺旋以接近开放状态推断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。
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 downshock. Among them, MscL has been intensively studied since the original identification and characterization 15 years ago by Kung and co-workers. MscL is reversibly and directly gated by changes in membrane tension. In the open state, MscL forms a nonselective 3 nS-conductance channel which gates at tensions close to the lytic limit of the bacterial membrane. An earlier crystal structure at 3.5 Å resolution of a pentameric MscL from Mycobacterium tuberculosis (TbMscL) represents a closed-state or nonconducting conformation. MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative nonconductive expanded state and at least three sub-conducting states. Although our understanding of the closed 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 truncation mutant (Δ95-120) of MscL from Staphylococcus aureus (SaMscL-CΔ26) at 3.8 Å resolution. Strikingly, SaMscL-CΔ26 forms a tetrameric channel with both transmembrane (TM) helices tilted away from the membrane normal at angles close to that inferred for the open state, likely corresponding to a nonconductive but partially expanded intermediate state.
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影响因子：
5.8
作者：
Gouet, P;Courcelle, E;Métoz, F
通讯作者：
Métoz, F
影响因子：
2
作者：
Beckstein, O;Sansom, MSP
通讯作者：
Sansom, MSP
DOI：
10.1107/s0108767386099622
发表时间：
1986-05-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION A
影响因子：
--
作者：
READ, RJ
通讯作者：
READ, RJ
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.
影响因子：
4.8
作者：
Ajouz, B;Berrier, C;Ghazi, E
通讯作者：
Ghazi, E