期刊
TOXINS
卷 12, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/toxins12080481
关键词
toxin-antitoxin; M; tuberculosis; bacteria; pathogenesis; protein-protein interactions; cross-talk; protein interface
资金
- Government of India-MHRD (Ministry of Human Resource Development)
- DST-FIST (Department of Science and Technology-Fund for improvement of S and T infrastructure)
- UGC (University Grants Commission) Center for Advanced Study
- Mathematical Biology program of the Department of Science and Technology
- DBT-IISc (Department of Biotechnology-Indian Institute of Science) Partnership Program
- DBT-COE (Department of Biotechnology-Centre of Excellence)
- CEFIPRA
- DBT-IISc partnership program
Mycobacterium tuberculosisgenome encodes over 80 toxin-antitoxin (TA) systems. While each toxin interacts with its cognate antitoxin, the abundance of TA systems presents an opportunity for potential non-cognate interactions. TA systems mediate manifold interactions to manage pathogenicity and stress response network of the cell and non-cognate interactions may play vital roles as well. To address if non-cognate and heterologous interactions are feasible and to understand the structural basis of their interactions, we have performed comprehensive computational analyses on the available 3D structures and generated structural models of paralogousM. tuberculosisVapBC and MazEF TA systems. For a majority of the TA systems, we show that non-cognate toxin-antitoxin interactions are structurally incompatible except for complexes like VapBC15 and VapBC11, which show similar interfaces and potential for cross-reactivity. For TA systems which have been experimentally shown earlier to disfavor non-cognate interactions, we demonstrate that they are structurally and stereo-chemically incompatible. For selected TA systems, our detailed structural analysis identifies specificity conferring residues. Thus, our work improves the current understanding of TA interfaces and generates a hypothesis based on congenial binding site, geometric complementarity, and chemical nature of interfaces. Overall, our work offers a structure-based explanation for non-cognate toxin-antitoxin interactions inM. tuberculosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据