Department of Microbiology, University of Washington, Seattle, WA 98195, United States.
Department of Bioengineering, University of Washington, Seattle, WA 98115, United States.
J Mol Biol. 2022 Sep 15;434(17):167717. doi: 10.1016/j.jmb.2022.167717. Epub 2022 Jul 4.
Allosteric proteins transition between 'inactive' and 'active' states. In general, such proteins assume distinct conformational states at the level of secondary, tertiary and/or quaternary structure. Different conformers of an allosteric protein can be antigenically dissimilar and induce antibodies with a highly distinctive specificities and neutralizing functional effects. Here we summarize studies on various functional types of monoclonal antibodies obtained against different allosteric conformers of the mannose-specific bacterial adhesin FimH - the most common cell attachment protein of Escherichia coli and other enterobacterial pathogens. Included are types of antibodies that activate the FimH function via interaction with ligand-induced binding sites or by wedging between domains as well as antibodies that inhibit FimH through orthosteric, parasteric, or novel dynasteric mechanisms. Understanding the molecular mechanism of antibody action against allosteric proteins provides insights on how to design antibodies with a desired functional effect, including those with neutralizing activity against bacterial and viral cell attachment proteins.
变构蛋白在“非活性”和“活性”状态之间转换。通常，此类蛋白在二级、三级和/或四级结构水平上呈现出不同的构象状态。变构蛋白的不同构象可以具有不同的抗原性，并诱导具有高度独特特异性和中和功能效应的抗体。在这里，我们总结了针对甘露糖特异性细菌黏附素 FimH 的不同变构构象获得的各种功能类型的单克隆抗体的研究 - FimH 是大肠杆菌和其他肠杆菌病原体中最常见的细胞附着蛋白。其中包括通过与配体诱导的结合位点相互作用或通过在结构域之间楔入来激活 FimH 功能的抗体，以及通过变构、变构或新的动力学机制抑制 FimH 的抗体。了解针对变构蛋白的抗体作用的分子机制为设计具有所需功能效果的抗体提供了思路，包括针对细菌和病毒细胞附着蛋白具有中和活性的抗体。
