Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH-Allianz, Germany.
Biochem J. 2010 Apr 14;427(3):523-34. doi: 10.1042/BJ20091005.
SPP (signal peptide peptidase) is an aspartyl intramembrane cleaving protease, which processes a subset of signal peptides, and is linked to the quality control of ER (endoplasmic reticulum) membrane proteins. We analysed SPP interactions with signal peptides and other membrane proteins by co-immunoprecipitation assays. We found that SPP interacts specifically and tightly with a large range of newly synthesized membrane proteins, including signal peptides, preproteins and misfolded membrane proteins, but not with all co-expressed type II membrane proteins. Signal peptides are trapped by the catalytically inactive SPP mutant SPPD/A. Preproteins and misfolded membrane proteins interact with both SPP and the SPPD/A mutant, and are not substrates for SPP-mediated intramembrane proteolysis. Proteins interacting with SPP are found in distinct complexes of different sizes. A signal peptide is mainly trapped in a 200 kDa SPP complex, whereas a preprotein is predominantly found in a 600 kDa SPP complex. A misfolded membrane protein is detected in 200, 400 and 600 kDa SPP complexes. We conclude that SPP not only processes signal peptides, but also collects preproteins and misfolded membrane proteins that are destined for disposal.
SPP（信号肽肽酶）是一种天冬氨酸跨膜裂解蛋白酶，可加工一部分信号肽，并与内质网（ER）膜蛋白的质量控制有关。我们通过共免疫沉淀分析研究了 SPP 与信号肽和其他膜蛋白的相互作用。我们发现，SPP 特异性且紧密地与多种新合成的膜蛋白相互作用，包括信号肽、前体蛋白和错误折叠的膜蛋白，但不与所有共表达的 II 型膜蛋白相互作用。催化失活的 SPPD/A 突变体可捕获信号肽。前体蛋白和错误折叠的膜蛋白与 SPP 和 SPPD/A 突变体相互作用，并且不是 SPP 介导的跨膜蛋白水解的底物。与 SPP 相互作用的蛋白质存在于不同大小的不同复合物中。信号肽主要被捕获在 200 kDa 的 SPP 复合物中，而前体蛋白主要存在于 600 kDa 的 SPP 复合物中。错误折叠的膜蛋白在 200、400 和 600 kDa 的 SPP 复合物中均有检测到。我们得出的结论是，SPP 不仅加工信号肽，还收集前体蛋白和注定要被处理的错误折叠的膜蛋白。
