Kassenbrock C K, Garcia P D, Walter P, Kelly R B
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Nature. 1988 May 5;333(6168):90-3. doi: 10.1038/333090a0.
Immunoglobulin heavy-chain binding protein (BiP, GRP-78) associates tightly in the endoplasmic reticulum (ER) with newly synthesized proteins that are incompletely assembled, have mutant structures, or are incorrectly glycosylated. The function of BiP has been suggested to be to prevent secretion of incorrectly folded or incompletely assembled protein, to promote folding or assembly of proteins, or to solubilize protein aggregates within the ER lumen. Here we examine the interaction of BiP with newly synthesized polypeptides in an in vitro protein translation-translocation system. We find that BiP forms tight complexes with nonglycosylated yeast invertase and incorrectly disulphide-bonded prolactin, but does not associate detectably with either glycosylated invertase or correctly disulphide-bonded prolactin. Moreover, BiP associates detectably only with completed chains of prolactin, not with chains undergoing synthesis. We conclude that BiP recognizes and binds with high affinity in vitro to aberrantly folded or aberrantly glycosylated polypeptides, but not to all nascent chains as they are folding.
免疫球蛋白重链结合蛋白（BiP，GRP - 78）在内质网（ER）中与新合成的、未完全组装、具有突变结构或糖基化错误的蛋白质紧密结合。BiP的功能被认为是防止错误折叠或未完全组装的蛋白质分泌，促进蛋白质折叠或组装，或溶解内质网腔中的蛋白质聚集体。在这里，我们在体外蛋白质翻译 - 转运系统中研究BiP与新合成多肽的相互作用。我们发现BiP与非糖基化酵母蔗糖酶和二硫键错误连接的催乳素形成紧密复合物，但与糖基化蔗糖酶或二硫键正确连接的催乳素均未检测到结合。此外，BiP仅与完整的催乳素链可检测到结合，而不与正在合成的链结合。我们得出结论，BiP在体外以高亲和力识别并结合异常折叠或异常糖基化的多肽，但不与所有正在折叠的新生链结合。
