Structure formation during translocon-unassisted co-translational membrane protein folding.
Structure formation during translocon-unassisted co-translational membrane protein folding.
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DOI：
10.1038/s41598-017-08522-9
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发表时间：
2017-08-14
影响因子：
4.6
通讯作者：
Booth PJ
中科院分区：
文献类型：
--
作者：
Harris NJ;Reading E;Ataka K;Grzegorzewski L;Charalambous K;Liu X;Schlesinger R;Heberle J;Booth PJ
正确折叠的膜蛋白是大量细胞过程的基础，但人们对它们如何折叠知之甚少。折叠机制的知识集中在化学变性膜蛋白的可逆折叠。然而，这不能在细胞中的共翻译折叠期间复制蛋白质链的单向伸长，其中插入由移位酶装置辅助。我们发现，脂膜（缺乏转位酶成分）是足够的成功的共翻译折叠的两个细菌α-螺旋膜蛋白，DsbB和GlpG。折叠是自发的，由脂质驱动，并且产量取决于脂质组成。时间分辨结构的形成过程中的共翻译折叠揭示了不同的二级和三级结构的折叠途径GlpG和DsbB与膜界面和生物跨膜氨基酸疏水性尺度。试图将DsbB和GlpG从化学变性状态重折叠成脂质膜导致广泛的聚集。因此，共翻译插入和折叠是自发的，并使聚集最小化，同时使正确折叠最大化。
Correctly folded membrane proteins underlie a plethora of cellular processes, but little is known about how they fold. Knowledge of folding mechanisms centres on reversible folding of chemically denatured membrane proteins. However, this cannot replicate the unidirectional elongation of the protein chain during co-translational folding in the cell, where insertion is assisted by translocase apparatus. We show that a lipid membrane (devoid of translocase components) is sufficient for successful co-translational folding of two bacterial α-helical membrane proteins, DsbB and GlpG. Folding is spontaneous, thermodynamically driven, and the yield depends on lipid composition. Time-resolving structure formation during co-translational folding revealed different secondary and tertiary structure folding pathways for GlpG and DsbB that correlated with membrane interfacial and biological transmembrane amino acid hydrophobicity scales. Attempts to refold DsbB and GlpG from chemically denatured states into lipid membranes resulted in extensive aggregation. Co-translational insertion and folding is thus spontaneous and minimises aggregation whilst maximising correct folding.
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影响因子：
3.7
作者：
Di Bartolo N;Compton EL;Warne T;Edwards PC;Tate CG;Schertler GF;Booth PJ
通讯作者：
Booth PJ
影响因子：
2.9
作者：
Curran, AR;Templer, RH;Booth, PJ
通讯作者：
Booth, PJ
影响因子：
5.6
作者：
Allen, SJ;Curran, AR;Booth, PJ
通讯作者：
Booth, PJ
影响因子：
3.3
作者：
Karjalainen, Eeva-Liisa;Barth, Andreas
通讯作者：
Barth, Andreas
影响因子：
5.6
作者：
Allen, SJ;Curran, AR;Booth, PJ
通讯作者：
Booth, PJ