Ojcius D M, Persechini P M, Zheng L M, Notaroberto P C, Adeodato S C, Young J D
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4621-5. doi: 10.1073/pnas.88.11.4621.
Perforin lyses cells by binding to the target cell membrane, where it polymerizes into large nonspecific pores. It is shown here that the first 34 amino acids of the N-terminal region of either human or murine perforin are soluble in aqueous medium and spontaneously insert into membranes. The N-terminal peptides lyse liposomes and nucleated cells, and they form ion channels in planar bilayers, some of which are comparable to those previously described for perforin. The lytic activity of the N-terminal domains does not require calcium, is independent of the lipid headgroup composition, and can be inhibited by heparin. Tumor cells incubated with the N-terminal peptides undergo the same morphological changes as those induced by native perforin. None of the peptides corresponding to the putative membrane-spanning domains from the central region of perforin is cytolytic. Taken together, these results suggest that the N-terminal region is an important part of the pore-forming domain of perforin.
穿孔素通过与靶细胞膜结合来裂解细胞，在靶细胞膜上它会聚合成大的非特异性孔道。本文表明，人或小鼠穿孔素N端区域的前34个氨基酸可溶于水性介质，并能自发插入膜中。N端肽可裂解脂质体和有核细胞，并且它们在平面双层膜中形成离子通道，其中一些离子通道与先前描述的穿孔素形成的离子通道相当。N端结构域的裂解活性不需要钙，与脂质头部基团组成无关，并且可被肝素抑制。用N端肽孵育的肿瘤细胞会发生与天然穿孔素诱导的相同形态变化。穿孔素中央区域假定的跨膜结构域对应的肽均无细胞溶解作用。综上所述，这些结果表明N端区域是穿孔素成孔结构域的重要组成部分。
