Structural studies of Streptococcus pyogenes streptolysin O provide insights into the early steps of membrane penetration.
Structural studies of Streptococcus pyogenes streptolysin O provide insights into the early steps of membrane penetration.
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DOI：
10.1016/j.jmb.2013.11.020
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发表时间：
2014-02-20
影响因子：
5.6
通讯作者：
Parker, Michael W.
中科院分区：
文献类型：
--
作者：
Feil, Susanne C.;Ascher, David B.;Kuiper, Michael J.;Tweten, Rodney K.;Parker, Michael W.
关键词：
胆固醇依赖的细胞溶血素(CDCs)是一大类细菌毒素，在细胞膜上形成大孔时依赖于膜胆固醇的存在。这些毒素的三维结构的显著变化是将可溶性单体蛋白转化为膜孔所必需的。我们已经确定了CDC家族的典型成员--化脓性链球菌的毒力因子--溶链素O(SLO)的晶体结构。整体折叠类似于以前报道的CDC结构，尽管C-末端结构域相对于分子的其余部分具有不同的取向。令人惊讶的是，CDC序列的一个标志性片段称为十一肽基序，这是参与膜识别的关键区域，它在SLO中采用了与特征良好的CDC产气相溶素O(PFO)非常不同的结构，尽管该区域的序列是相同的。分析表明，在PFO中，基序与SLO中丢失的第4结构域之间存在互补的相互作用。分子动力学模拟表明，SLO中盐桥的丧失和阳离子-pi相互作用是该基序延伸构象的决定因素，这反过来似乎导致邻近的L1环具有更大的灵活性，其中包含一个胆固醇敏感基序。这些差异可能解释了SLO和PFO在毒素插入膜的第一步有效穿透靶细胞膜的不同能力。
Cholesterol-dependent cytolysins (CDCs) are a large family of bacterial toxins that exhibit a dependence on the presence of membrane cholesterol in forming large pores in cell membranes. Significant changes in the three-dimensional structure of these toxins are necessary to convert the soluble monomeric protein into a membrane pore. We have determined the crystal structure of the archetypical member of the CDC family, streptolysin O (SLO), a virulence factor from Streptococcus pyogenes. The overall fold is similar to previously reported CDC structures, although the C-terminal domain is in a different orientation with respect to the rest of the molecule. Surprisingly, a signature stretch of CDC sequence called the undecapeptide motif, a key region involved in membrane recognition, adopts a very different structure in SLO to that of the well-characterized CDC perfringolysin O (PFO), although the sequences in this region are identical. An analysis reveals that, in PFO, there are complementary interactions between the motif and the rest of domain 4 that are lost in SLO. Molecular dynamics simulations suggest that the loss of a salt bridge in SLO and a cation–pi interaction are determining factors in the extended conformation of the motif, which in turn appears to result in a greater flexibility of the neighboring L1 loop that houses a cholesterol-sensing motif. These differences may explain the differing abilities of SLO and PFO to efficiently penetrate target cell membranes in the first step of toxin insertion into the membrane.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.9
作者：
DOURMASHKIN, RR;ROSSE, WF
通讯作者：
ROSSE, WF
影响因子：
7.8
作者：
DUNCAN, JL;SCHLEGEL, R
通讯作者：
SCHLEGEL, R
DOI：
10.1107/s0907444902016657
发表时间：
2002-11-01
影响因子：
2.2
作者：
Adams, PD;Grosse-Kunstleve, RW;Terwilliger, TC
通讯作者：
Terwilliger, TC
影响因子：
64.5
作者：
Madden, JC;Ruiz, N;Caparon, M
通讯作者：
Caparon, M