Lukoyanova Natalya, Hoogenboom Bart W, Saibil Helen R
Department of Crystallography/Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
London Centre for Nanotechnology, University College London, London WC1H 0AH, UK Department of Physics and Astronomy, University College London, London WC1E 6BT, UK.
J Cell Sci. 2016 Jun 1;129(11):2125-33. doi: 10.1242/jcs.182741. Epub 2016 May 13.
The membrane attack complex and perforin proteins (MACPFs) and bacterial cholesterol-dependent cytolysins (CDCs) are two branches of a large and diverse superfamily of pore-forming proteins that function in immunity and pathogenesis. During pore formation, soluble monomers assemble into large transmembrane pores through conformational transitions that involve extrusion and refolding of two α-helical regions into transmembrane β-hairpins. These transitions entail a dramatic refolding of the protein structure, and the resulting assemblies create large holes in cellular membranes, but they do not use any external source of energy. Structures of the membrane-bound assemblies are required to mechanistically understand and modulate these processes. In this Commentary, we discuss recent advances in the understanding of assembly mechanisms and molecular details of the conformational changes that occur during MACPF and CDC pore formation.
膜攻击复合物与穿孔素蛋白（MACPFs）以及细菌胆固醇依赖细胞溶素（CDCs）是一个庞大且多样的成孔蛋白超家族的两个分支，它们在免疫和发病机制中发挥作用。在形成孔的过程中，可溶性单体通过构象转变组装成大型跨膜孔，该转变涉及将两个α-螺旋区域挤出并重新折叠成跨膜β-发夹。这些转变需要蛋白质结构进行剧烈的重新折叠，并且形成的组装体在细胞膜上产生大洞，但它们不使用任何外部能量来源。需要膜结合组装体的结构来从机制上理解和调节这些过程。在本评论中，我们讨论了在理解MACPF和CDC孔形成过程中发生的组装机制和构象变化分子细节方面的最新进展。
