Department of Chemistry, University of Oxford, Oxford OX1 3TA, United Kingdom.
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2425-30. doi: 10.1073/pnas.1312976111. Epub 2014 Jan 27.
Membrane proteins are generally divided into two classes. Integral proteins span the lipid bilayer, and peripheral proteins are located at the membrane surface. Here, we provide evidence for membrane proteins of a third class that stabilize lipid pores, most probably as toroidal structures. We examined mutants of the staphylococcal α-hemolysin pore so severely truncated that the protein cannot span a bilayer. Nonetheless, the doughnut-like structures elicited well-defined transmembrane ionic currents by inducing pore formation in the underlying lipids. The formation of lipid pores, produced here by a structurally defined protein, is supported by the lipid and voltage dependences of pore formation, and by molecular dynamics simulations. We discuss the role of stabilized lipid pores in amyloid disease, the action of antimicrobial peptides, and the assembly of the membrane-attack complexes of the immune system.
膜蛋白通常分为两类。整合蛋白贯穿脂双层，而外周蛋白位于膜表面。在这里，我们提供了第三类稳定脂孔的膜蛋白的证据，这些蛋白很可能作为环形结构存在。我们研究了葡萄球菌α-溶血素孔的突变体，这些突变体严重截断，以至于蛋白质无法跨越双层。尽管如此，这些甜甜圈状结构通过在下面的脂质中诱导孔形成，引发了明确的跨膜离子电流。由结构定义的蛋白质产生的脂孔的形成，得到了孔形成的脂质和电压依赖性以及分子动力学模拟的支持。我们讨论了稳定的脂孔在淀粉样疾病、抗菌肽的作用以及免疫系统的膜攻击复合物组装中的作用。
