Collier D N, Bassford P J
Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill 27599-7290.
J Bacteriol. 1989 Sep;171(9):4640-7. doi: 10.1128/jb.171.9.4640-4647.1989.
It previously has been proposed that the Escherichia coli SecB protein promotes the export of the maltose-binding protein (MBP) from the cytoplasm by preventing the folding of the precursor MBP (preMBP) into a translocation-incompetent conformation. The export of wild-type MBP is only partially blocked in SecB- cells. In contrast, the export of MBP16-1, an MBP species with a defective signal peptide, is totally dependent on SecB; hence, SecB- cells that synthesize MBP16-1 are unable to utilize maltose as a sole carbon source. The selection of Mal+ revertants primarily yielded mutants with alterations in the MBP16-1 signal peptide that permitted SecB-independent MBP export to the periplasm to various extents. Although each of these alterations increased the overall hydrophobicity of the signal peptide, it was not possible to strictly equate changes in hydrophobicity with the degree of SecB-independent export. Somewhat unexpectedly, two mutants were obtained in which MBP export in SecB- cells was markedly superior to that of the wild-type MBP. Although wild-type MBP is not cotranslationally translocated in SecB- cells, the two mutant proteins designated MBP172 and MBP173 exhibited significant cotranslational export in the absence of SecB. Thus, the role of SecB was partially supplanted by a signal peptide that promoted more rapid movement of MBP through the export pathway. When preMBP included the MBP172 signal peptide as well as an alteration in the mature moiety that slows folding, the SecB requirement for maximal MBP export efficiency was almost totally eliminated. These results provide additional strong support for the proposed antifolding role of SecB in MBP export.
此前有人提出,大肠杆菌SecB蛋白通过防止前体麦芽糖结合蛋白(preMBP)折叠成无法转运的构象,促进麦芽糖结合蛋白(MBP)从细胞质中输出。野生型MBP的输出在SecB缺陷型细胞中仅被部分阻断。相比之下,MBP16-1(一种信号肽有缺陷的MBP变体)的输出则完全依赖于SecB;因此,合成MBP16-1的SecB缺陷型细胞无法利用麦芽糖作为唯一碳源。Mal+回复突变体的筛选主要产生了信号肽发生改变的突变体,这些突变体在不同程度上允许MBP在不依赖SecB的情况下输出到周质。尽管这些改变中的每一个都增加了信号肽的整体疏水性,但无法将疏水性的变化与不依赖SecB的输出程度严格等同起来。有点出乎意料的是,获得了两个突变体,其中SecB缺陷型细胞中的MBP输出明显优于野生型MBP。尽管野生型MBP在SecB缺陷型细胞中不会共翻译转运,但命名为MBP172和MBP173的这两个突变蛋白在没有SecB的情况下表现出显著的共翻译输出。因此,SecB的作用被一个信号肽部分取代,该信号肽促进MBP更快地通过输出途径移动。当preMBP包含MBP172信号肽以及成熟部分的一个减缓折叠的改变时,最大MBP输出效率对SecB的需求几乎完全消除。这些结果为SecB在MBP输出中所提出的抗折叠作用提供了额外的有力支持。