PROTEIN TRANSLOCATION ACROSS THE ENDOPLASMIC-RETICULUM
PROTEIN TRANSLOCATION ACROSS THE ENDOPLASMIC-RETICULUM
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DOI：
10.1016/0092-8674(84)90520-8
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发表时间：
1984-01-01
期刊：
影响因子：
64.5
通讯作者：
BLOBEL, G
中科院分区：
文献类型：
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作者：
WALTER, P;GILMORE, R;BLOBEL, G
蛋白质生物合成的一个重要方面是它们的细胞内拓扑结构（Blobel, PNAS 77, 1496, 1980）。许多蛋白质一生都待在合成它们的同一个隔间里；另一些则必须穿过不同细胞膜的疏水屏障，才能到达细胞内或细胞外的位置，在那里它们发挥作用。许多膜蛋白必须不对称地整合到不同的细胞膜上。对于许多这样的蛋白质来说，这需要部分易位，即多肽链的不同亲水性结构域在特定膜上的选择性转移。因此，细胞中必须存在一种机制，以确保这些蛋白质被靶向并随后在正确的细胞膜上转移，而细胞膜本身仍然不被其他溶质渗透。在过去的几年中，我们对内质网（ER）的靶向和转运机制的理解取得了重大进展。三种不同类型的蛋白质利用这种易位系统：分泌蛋白（Palade, Science 789, 347, 1975）和溶酶体蛋白（Erickson等，JBC 256, 11224, 1981）被跨易位，而某些类型的整体膜蛋白（Lingappa等，JBC 253, 8667, 1978）被整合到内质网膜中。通过体外系统的开发，对这一过程进行详细的生化分析变得可行，该系统能够再现新生分泌蛋白在内质网膜上的易位（以封闭微粒体囊泡的形式分离），并具有明显的保真度（Blobel和Dobberstein， JCB 67, 852, 1975； Szczesna和Boime， PNAS 73, 1179, 1976）。到目前为止，已经从犬胰腺中纯化了两种成分，并证明了易位事件所必需的。其中一种成分是信号识别粒子（SRP），一种11s细胞质核糖核蛋白。SRP由6个不同的多肽链组成，表观分子量分别为72、68、54、19、14和9kd （Walter and Blobel, PNAS 77、7112,1980）和1个RNA分子（Walter and Blobel, Nature 299、691,1982）。当分离时，RNA和蛋白质都是无活性的，但它们可以很容易地重组成活性颗粒（Walter和Blobel， Cell 34, 525, 1983）。
An important aspect of the biosynthesis of proteins is their intracellular topology (Blobel, PNAS 77, 1496, 1980). Many proteins spend their entire lives in the same compartment in which they were synthesized; others have to cross the hydrophobic barrier of distinct cellular membranes in order to reach an intracellular compartment or extracellular site where they exert their function. Numerous membrane proteins have to be integrated asymmetrically into distinct cellular membranes. For many of these proteins this requires partial translocation, ie, the selective transfer of distinct hydrophilic domains of their polypeptide chain across specific membranes. Thus mechanisms must exist in the cell that assure that these proteins are targeted to, and subsequently translocated across, the correct intracellular membrane, while the membrane itself remains impermeable to other solutes. In the last few years major advances have been made in our understanding of the targeting and translocation machinery of the endoplasmic reticulum (ER). Three distinct classes of proteins utilize this translocation system: secretory proteins (Palade, Science 789, 347, 1975) and lysosomal proteins (Erickson et al., JBC 256, 11224, 1981) are translocated across, while certain classes of integral membrane proteins (Lingappa et al., JBC 253, 8667, 1978) are integrated into, the ER membrane. A detailed biochemical analysis of this process became feasible through the development of in vitro systems that were able to reproduce the translocation of nascent secretory proteins across the ER membrane (isolated in the form of closed microsomal vesicles) with apparent fidelity (Blobel and Dobberstein, JCB 67, 852, 1975; Szczesna and Boime, PNAS 73, 1179, 1976). So far, two components have been purified from canine pancreas and shown to be required for the translocation event.One of these components is the signal recognition particle (SRP), an 11 S cytoplasmic ribonucleoprotein. SRP consists of six nonidentical polypeptide chains with apparent molecular weights of 72, 68, 54, 19, 14, and 9 kd (Walter and Blobel, PNAS 77, 7112, 1980) and one molecule of RNA of about 300 nucleotides (Walter and Blobel, Nature 299, 691, 1982). When separated, both RNA and proteins are inactive, but they can be readily reconstituted into an active particle (Walter and Blobel, Cell 34, 525, 1983).