Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins
Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins
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DOI：
10.1016/s0092-8674(04)00169-2
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发表时间：
2004-03-05
期刊：
影响因子：
64.5
通讯作者：
Johnson, AE
中科院分区：
文献类型：
--
作者：
Woolhead, CA;McCormick, PJ;Johnson, AE
荧光共振能量转移测量表明，一个新生的膜蛋白内的跨膜序列折叠成一个紧凑的构象附近的肽基转移酶中心，并保持折叠的序列移动通过膜结合的核糖体进入易位子。这种紧凑的构象与α螺旋相容，因为当跨膜序列整合到脂质双层中时观察到几乎相同的能量转移效率。由于跨膜序列在从游离核糖体出现时展开，因此这种新生链折叠是核糖体诱导和稳定的。相反，新生分泌蛋白在出口通道中处于延伸构象。此外，两个核糖体蛋白质光交联新生膜，但不是分泌蛋白。这些相互作用与先前描述的顺序关闭和开放的两端的水translocon孔，从而表明，核糖体识别新生链折叠控制的操作模式的translocon在ER膜。
Fluorescence resonance energy transfer measurements reveal that a transmembrane sequence within a nascent membrane protein folds into a compact conformation near the peptidyltransferase center and remains folded as the sequence moves through a membrane bound ribosome into the translocon. This compact conformation is compatible with an alpha helix because nearly the same energy transfer efficiency was observed when the transmembrane sequence was integrated into the lipid bilayer. Since the transmembrane sequence unfolds upon emerging from a free ribosome, this nascent chain folding is ribosome induced and stabilized. In contrast, a nascent secretory protein is in an extended conformation in the exit tunnel. Furthermore, two ribosomal proteins photo-crosslink to nascent membrane but not secretory proteins. These interactions coincide with the previously described sequential closing and opening of the two ends of the aqueous translocon pore, thereby suggesting that ribosomal recognition of nascent chain folding controls the operational mode of the translocon at the ER membrane.