Pollitt N S, Inouye M
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry, Piscataway, New Jersey 08854-5635.
J Bacteriol. 1988 May;170(5):2051-5. doi: 10.1128/jb.170.5.2051-2055.1988.
A deletion mutation (lpp delta 9 delta 13 delta 14) in the signal peptide of the major outer membrane lipoprotein of Escherichia coli (Lpp) was found to cause severe effects on cell physiology, resulting in cessation of growth within 10 min of induction of lpp delta 9 delta 13 delta 14 expression and rapid cell death. Further investigation revealed that lpp delta 9 delta 13 delta 14 expression caused slow processing of several other exported proteins. The origin of this effect was traced to depolarization of the electrochemical potential across the cytoplasmic membrane, which is known to be required for efficient protein export. Analysis of the processing rate of the mutant, either prior to complete depolarization or in a suppressor strain in which depolarization does not occur, indicates that the mutant protein was capable of secretion at a rate which, while less than that of the wild type, was reasonably rapid compared with the rates of other E. coli secreted proteins. The existence of this type of signal peptide mutation suggests that the cell may have a mechanism to avoid membrane damage from secretory proteins carrying membrane-active signal peptides which is bypassed by the lpp delta 9 delta 13 delta 14 mutant.
研究发现，大肠杆菌（Escherichia coli）主要外膜脂蛋白（Lpp）信号肽中的一个缺失突变（lpp delta 9 delta 13 delta 14）对细胞生理产生严重影响，导致在诱导lpp delta 9 delta 13 delta 14表达后10分钟内生长停止并迅速细胞死亡。进一步研究表明，lpp delta 9 delta 13 delta 14的表达导致其他几种输出蛋白的加工缓慢。这种效应的根源可追溯到跨细胞质膜的电化学电位去极化，而高效的蛋白质输出需要这种电位。对突变体在完全去极化之前或在未发生去极化的抑制菌株中的加工速率分析表明，突变蛋白能够以一定速率分泌，虽然该速率低于野生型，但与其他大肠杆菌分泌蛋白的速率相比仍相当快。这种信号肽突变类型的存在表明，细胞可能有一种机制来避免携带膜活性信号肽的分泌蛋白造成的膜损伤，而lpp delta 9 delta 13 delta 14突变体绕过了这一机制。
