Lacy D B, Collier R J
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Curr Top Microbiol Immunol. 2002;271:61-85. doi: 10.1007/978-3-662-05767-4_4.
Anthrax toxin is a binary A-B toxin comprised of protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF). In the presence of a host cell-surface receptor, PA can mediate the delivery of EF and LF from the extracellular milieu into the host cell cytosol to effect toxicity. In this delivery, PA undergoes multiple structural changes--from a monomer to a heptameric prepore to a membrane-spanning heptameric pore. The catalytic factors also undergo dramatic structural changes as they unfold to allow for their translocation across the endosomal membrane and refold to preserve their catalytic activity within the cytosol. In addition to these gross structural changes, the intoxication mechanism depends on the ability of PA to form specific interactions with the host cell receptor, EF, and LF. This chapter presents a review of experiments probing these structural interactions and rearrangements in the hopes of gaining a molecular understanding of toxin action.
炭疽毒素是一种二元A-B毒素，由保护性抗原（PA）以及两种酶成分——水肿因子（EF）和致死因子（LF）组成。在宿主细胞表面受体存在的情况下，PA可介导EF和LF从细胞外环境转运至宿主细胞胞质溶胶中以发挥毒性作用。在这一转运过程中，PA会经历多种结构变化——从单体变为七聚体前体孔道，再变为跨膜七聚体孔道。催化因子在展开以允许其跨内体膜转运并重新折叠以在胞质溶胶中保持其催化活性时，也会经历显著的结构变化。除了这些总体结构变化外，中毒机制还取决于PA与宿主细胞受体、EF和LF形成特异性相互作用的能力。本章对探究这些结构相互作用和重排的实验进行了综述，以期从分子层面理解毒素的作用机制。
