Arolas Joan L, Goulas Theodoros, Pomerantsev Andrei P, Leppla Stephen H, Gomis-Rüth F Xavier
Proteolysis Lab, Department of Structural Biology ("María de Maeztu" Unit of Excellence), Molecular Biology Institute of Barcelona, Spanish Research Council (CSIC), Barcelona Science Park, Helix Building, Baldiri Reixac, 15-21, 08028 Barcelona, Spain.
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Structure. 2016 Jan 5;24(1):25-36. doi: 10.1016/j.str.2015.10.015.
Immune inhibitor A(InhA)-type metallopeptidases are potential virulence factors secreted by members of the Bacillus cereus group. Two paralogs from anthrax-causing Bacillus anthracis (BaInhA1 and BaInhA2) were shown to degrade host tissue proteins with broad substrate specificity. Analysis of their activation mechanism and the crystal structure of a zymogenic BaInhA2 variant revealed a ∼750-residue four-domain structure featuring a pro-peptide, a catalytic domain, a domain reminiscent of viral envelope glycoproteins, and a MAM domain grafted into the latter. This domain, previously found only in eukaryotes, is required for proper protein expression in B. anthracis and evinces certain flexibility. Latency is uniquely modulated by the N-terminal segment of the pro-peptide, which binds the catalytic zinc through its α-amino group and occupies the primed side of the active-site cleft. The present results further our understanding of the modus operandi of an anthrax secretome regulator.
免疫抑制剂A（InhA）型金属肽酶是蜡样芽孢杆菌属成员分泌的潜在毒力因子。来自引起炭疽病的炭疽芽孢杆菌的两个旁系同源物（BaInhA1和BaInhA2）被证明能降解具有广泛底物特异性的宿主组织蛋白。对其激活机制的分析以及酶原性BaInhA2变体的晶体结构揭示了一个约750个残基的四结构域结构，其特征包括一个前肽、一个催化结构域、一个类似于病毒包膜糖蛋白的结构域以及一个嫁接到后者中的MAM结构域。这个以前仅在真核生物中发现的结构域，对于炭疽芽孢杆菌中蛋白质的正确表达是必需的，并且表现出一定的灵活性。潜伏期由前肽的N末端片段独特地调节，该片段通过其α-氨基结合催化锌并占据活性位点裂隙的引发侧。目前的结果进一步加深了我们对炭疽分泌组调节剂作用方式的理解。
