Department of Chemistry, University of California, Berkeley, California, USA.
Nat Struct Mol Biol. 2010 Nov;17(11):1383-90. doi: 10.1038/nsmb.1923. Epub 2010 Oct 31.
The protein transporter anthrax lethal toxin is composed of protective antigen (PA), a transmembrane translocase, and lethal factor (LF), a cytotoxic enzyme. After its assembly into holotoxin complexes, PA forms an oligomeric channel that unfolds LF and translocates it into the host cell. We report the crystal structure of the core of a lethal toxin complex to 3.1-Å resolution; the structure contains a PA octamer bound to four LF PA-binding domains (LF(N)). The first α-helix and β-strand of each LF(N) unfold and dock into a deep amphipathic cleft on the surface of the PA octamer, which we call the α clamp. The α clamp possesses nonspecific polypeptide binding activity and is functionally relevant to efficient holotoxin assembly, PA octamer formation, and LF unfolding and translocation. This structure provides insight into the mechanism of translocation-coupled protein unfolding.
炭疽致死毒素的蛋白转运器由保护性抗原（PA）、跨膜转运酶和致死因子（LF）、一种细胞毒性酶组成。在组装成全毒素复合物后，PA 形成一个寡聚体通道，使 LF 展开并将其转运到宿主细胞中。我们报告了致死毒素复合物核心的晶体结构，分辨率为 3.1 Å；该结构包含一个与四个 LF PA 结合结构域（LF（N））结合的 PA 八聚体。每个 LF（N）的第一个α-螺旋和β-链展开并停靠在 PA 八聚体表面的一个深亲水头隙中，我们称之为α夹。α夹具有非特异性多肽结合活性，与有效全毒素组装、PA 八聚体形成以及 LF 展开和转运功能相关。该结构为易位偶联蛋白展开的机制提供了深入的了解。
