能够形成微孔的免疫蛋白“perforin”是消除被病毒感染的细胞及癌变细胞所必需的，由自然杀手及细胞毒性T-细胞释放。
现在，一种“perforin”单聚物（小鼠perforin R213E）的结构已被确定。对该结构所做分析同时结合对低聚孔的一个冷电子显微镜重建结果表明，这个孔内的“perforin”单聚物与依赖于*的溶细胞素在结构上同源的单聚物相比采用一种“内面向外”的取向。
这种新颖的适应性也许可解释“perforin”是怎样将支持细胞凋亡的蛋白酶（granzymes）送入目标细胞中的以及相关的互补免疫蛋白是怎样组装成微孔的。
英文摘要：
Nature doi:10.1038/nature09518
The structural basis for membrane binding and pore formation by lymphocyte perforin
Ruby H. P. Law,Natalya Lukoyanova,Ilia Voskoboinik,Tom T. Caradoc-Davies,Katherine Baran,Michelle A. Dunstone,Michael E. D'Angelo,Elena V. Orlova,Fasséli Coulibaly,Sandra Verschoor,Kylie A. Browne,Annette Ciccone,Michael J. Kuiper,Phillip I. Bird,Joseph A. Trapani,joe.trapani@Helen R. Saibil& James C. Whisstock
Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neoplastic cells. They do this by releasing the pore-forming protein perforin and granzyme proteases from cytoplasmic granules into the cleft formed between the abutting killer and target cell membranes. Perforin, a 67-kilodalton multidomain protein, oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell1, 2, 3, 4, 5, 6. The importance of perforin is highlighted by the fatal consequences of congenital perforin deficiency, with more than 50 different perforin mutations linked to familial haemophagocytic lymphohistiocytosis （type 2 FHL）7. Here we elucidate the mechanism of perforin pore formation by determining the X-ray crystal structure of monomeric murine perforin, together with a cryo-electron microscopy reconstruction of the entire perforin pore. Perforin is a thin 'key-shaped' molecule, comprising an amino-terminal membrane attack complex perforin-like （MACPF）/cholesterol dependent cytolysin （CDC） domain8, 9 followed by an epidermal growth factor （EGF） domain that, together with the extreme carboxy-terminal sequence, forms a central shelf-like structure. A C-terminal C2 domain mediates initial, Ca2+-dependent membrane binding. Most unexpectedly, however, electron microscopy reveals that the orientation of the perforin MACPF domain in the pore is inside-out relative to the subunit arrangement in CDCs10, 11. These data reveal remarkable flexibility in the mechanism of action of the conserved MACPF/CDC fold and provide new insights into how related immune defence molecules such as complement proteins assemble into pores.
