Mechaly A, Fierobe H P, Belaich A, Belaich J P, Lamed R, Shoham Y, Bayer E A
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
J Biol Chem. 2001 Mar 30;276(13):9883-8. doi: 10.1074/jbc.M009237200. Epub 2001 Jan 8.
The assembly of enzyme components into the cellulosome complex is dictated by the cohesin-dockerin interaction. In a recent article (Mechaly, A., Yaron, S., Lamed, R., Fierobe, H.-P., Belaich, A., Belaich, J.-P., Shoham, Y., and Bayer, E. A. (2000) Proteins 39, 170-177), we provided experimental evidence that four previously predicted dockerin residues play a decisive role in the specificity of this high affinity interaction, although additional residues were also implicated. In the present communication, we examine further the contributing factors for the recognition of a dockerin by a cohesin domain between the respective cellulosomal systems of Clostridium thermocellum and Clostridium cellulolyticum. In this context, the four confirmed residues were analyzed for their individual effect on selectivity. In addition, other dockerin residues were discerned that could conceivably contribute to the interaction, and the suspected residues were similarly modified by site-directed mutagenesis. The results indicate that mutation of a single residue from threonine to leucine at a given position of the C. thermocellum dockerin differentiates between its nonrecognition and high affinity recognition (K(a) approximately 10(9) m(-1)) by a cohesin from C. cellulolyticum. This suggests that the presence or absence of a single decisive hydroxyl group is critical to the observed biorecognition. This study further implicates additional residues as secondary determinants in the specificity of interaction, because interconversion of selected residues reduced intraspecies self-recognition by at least three orders of magnitude. Nevertheless, as the latter mutageneses served to reduce but not annul the cohesin-dockerin interaction within this species, it follows that other subtle alterations play a comparatively minor role in the recognition between these two modules.
酶组分组装到纤维小体复合物中是由内聚蛋白-锚定蛋白相互作用决定的。在最近的一篇文章(Mechaly, A., Yaron, S., Lamed, R., Fierobe, H.-P., Belaich, A., Belaich, J.-P., Shoham, Y., and Bayer, E. A. (2000) Proteins 39, 170 - 177)中,我们提供了实验证据,表明四个先前预测的锚定蛋白残基在这种高亲和力相互作用的特异性中起决定性作用,尽管其他残基也有涉及。在本通讯中,我们进一步研究了嗜热栖热梭菌和解纤维梭菌各自纤维小体系统中内聚蛋白结构域识别锚定蛋白的影响因素。在此背景下,分析了四个已确认的残基对选择性的各自影响。此外,还识别出其他可能有助于相互作用的锚定蛋白残基,并通过定点诱变对这些可疑残基进行了类似的修饰。结果表明,嗜热栖热梭菌锚定蛋白特定位置上的一个残基从苏氨酸突变为亮氨酸,可区分其不被解纤维梭菌的内聚蛋白识别与高亲和力识别(K(a)约为10(9) m(-1))。这表明单个决定性羟基的存在与否对观察到的生物识别至关重要。本研究进一步表明其他残基是相互作用特异性的次要决定因素,因为选定残基的相互转换使种内自我识别降低了至少三个数量级。然而,由于后一种诱变作用是减少而不是消除该物种内的内聚蛋白-锚定蛋白相互作用,因此可以得出结论,其他细微改变在这两个模块之间的识别中起相对较小的作用。