Graduate Biomedical Sciences Pathobiology, Physiology and Pharmacology Theme, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Toxins (Basel). 2024 Sep 19;16(9):406. doi: 10.3390/toxins16090406.
ABC toxin complexes are a class of protein toxin translocases comprised of a multimeric assembly of protein subunits. Each subunit displays a unique composition, contributing to the formation of a syringe-like nano-machine with natural cargo carrying, targeting, and translocation capabilities. Many of these toxins are insecticidal, drawing increasing interest in agriculture for use as biological pesticides. The A subunit (TcA) is the largest subunit of the complex and contains domains associated with membrane permeation and targeting. The B and C subunits, TcB and TcC, respectively, package into a cocoon-like structure that contains a toxic peptide and are coupled to TcA to form a continuous channel upon final assembly. In this review, we outline the current understanding and gaps in the knowledge pertaining to ABC toxins, highlighting seven published structures of TcAs and how these structures have led to a better understanding of the mechanism of host tropism and toxin translocation. We also highlight similarities and differences between homologues that contribute to variations in host specificity and conformational change. Lastly, we review the biotechnological potential of ABC toxins as both pesticides and cargo-carrying shuttles that enable the transport of peptides into cells.
ABC 毒素复合物是一类由蛋白质亚基组成的多聚体装配的蛋白毒素转位酶，每个亚基都有独特的组成，形成了一个类似注射器的纳米机器，具有天然货物携带、靶向和转位能力。许多这些毒素具有杀虫作用，在农业中越来越受到关注，可作为生物农药使用。A 亚基（TcA）是复合物中最大的亚基，包含与膜渗透和靶向相关的结构域。B 和 C 亚基，即 TcB 和 TcC，分别包装成一个茧状结构，其中包含有毒肽，并与 TcA 偶联，在最终组装时形成连续通道。在这篇综述中，我们概述了目前对 ABC 毒素的理解和知识空白，重点介绍了 7 个已发表的 TcA 结构，以及这些结构如何帮助更好地理解宿主嗜性和毒素转位的机制。我们还强调了同源物之间的相似性和差异，这些差异导致了宿主特异性和构象变化的差异。最后，我们综述了 ABC 毒素作为杀虫剂和货物载体穿梭物的生物技术潜力，这些毒素能够将肽类物质运输到细胞中。
