A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion.
A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion.
复制标题
DOI：
10.1038/srep38399
复制
发表时间：
2016-12-07
影响因子：
4.6
通讯作者：
Schaffitzel C
中科院分区：
文献类型：
--
作者：
Botte M;Zaccai NR;Nijeholt JL;Martin R;Knoops K;Papai G;Zou J;Deniaud A;Karuppasamy M;Jiang Q;Roy AS;Schulten K;Schultz P;Rappsilber J;Zaccai G;Berger I;Collinson I;Schaffitzel C
保守的SecYEG蛋白传导通道和辅助蛋白SecDF-YajC和YidC构成细菌全转位子（HTL），能够分泌蛋白和插入膜蛋白。通过采用小角中子散射（SANS），低分辨率电子显微镜和生物物理分析相结合的综合方法，我们确定了超复合物内的蛋白质和脂质的排列。这些结果指导了单个HTL组件的X射线结构的放置，并允许提出功能性易位子的模型。它们围绕着一个中央含脂池的排列传达了一个意想不到的，但令人信服的膜蛋白插入机制。YidC和SecD的周质结构域位于SecY的蛋白通道出口位点，可能有助于易位多肽的出现。用于膜插入的SecY侧门与膜“插入酶”YidC相邻。绝对规模的SANS采用一种新的对比度匹配点分析揭示了一个动态的复杂采用开放和紧凑的配置周围的一个适应性强的中央脂质填充室，其中多位膜蛋白可以折叠，从聚集和蛋白水解庇护。
The conserved SecYEG protein-conducting channel and the accessory proteins SecDF-YajC and YidC constitute the bacterial holo-translocon (HTL), capable of protein-secretion and membrane-protein insertion. By employing an integrative approach combining small-angle neutron scattering (SANS), low-resolution electron microscopy and biophysical analyses we determined the arrangement of the proteins and lipids within the super-complex. The results guided the placement of X-ray structures of individual HTL components and allowed the proposal of a model of the functional translocon. Their arrangement around a central lipid-containing pool conveys an unexpected, but compelling mechanism for membrane-protein insertion. The periplasmic domains of YidC and SecD are poised at the protein-channel exit-site of SecY, presumably to aid the emergence of translocating polypeptides. The SecY lateral gate for membrane-insertion is adjacent to the membrane ‘insertase’ YidC. Absolute-scale SANS employing a novel contrast-match-point analysis revealed a dynamic complex adopting open and compact configurations around an adaptable central lipid-filled chamber, wherein polytopic membrane-proteins could fold, sheltered from aggregation and proteolysis.