Faculty of Agriculture, Sylhet Agricultural University, Sylhet, Bangladesh.
Department of Biochemistry and Chemistry, Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, Bangladesh.
PLoS Comput Biol. 2022 Jun 16;18(6):e1009539. doi: 10.1371/journal.pcbi.1009539. eCollection 2022 Jun.
Accelerated cell death 11 (ACD11) is an autoimmune gene that suppresses pathogen infection in plants by preventing plant cells from becoming infected by any pathogen. This gene is widely known for growth inhibition, premature leaf chlorosis, and defense-related programmed cell death (PCD) in seedlings before flowering in Arabidopsis plant. Specific amino acid changes in the ACD11 protein's highly conserved domains are linked to autoimmune symptoms including constitutive defensive responses and necrosis without pathogen awareness. The molecular aspect of the aberrant activity of the ACD11 protein is difficult to ascertain. The purpose of our study was to find the most deleterious mutation position in the ACD11 protein and correlate them with their abnormal expression pattern. Using several computational methods, we discovered PCD vulnerable single nucleotide polymorphisms (SNPs) in ACD11. We analysed the RNA-Seq data, identified the detrimental nonsynonymous SNPs (nsSNP), built genetically mutated protein structures and used molecular docking to assess the impact of mutation. Our results demonstrated that the A15T and A39D mutations in the GLTP domain were likely to be extremely detrimental mutations that inhibit the expression of the ACD11 protein domain by destabilizing its composition, as well as disrupt its catalytic effectiveness. When compared to the A15T mutant, the A39D mutant was more likely to destabilize the protein structure. In conclusion, these mutants can aid in the better understanding of the vast pool of PCD susceptibilities connected to ACD11 gene GLTP domain activation.
加速细胞死亡 11(ACD11)是一种自身免疫基因,通过防止植物细胞被任何病原体感染,从而抑制植物病原体感染。该基因在拟南芥植物开花前的幼苗中,因其生长抑制、过早的叶片黄化和与防御相关的程序性细胞死亡(PCD)而广为人知。ACD11 蛋白高度保守结构域中的特定氨基酸变化与自身免疫症状有关,包括无病原体感知的组成性防御反应和坏死。ACD11 蛋白异常活性的分子方面很难确定。我们的研究目的是找到 ACD11 蛋白中最具破坏性的突变位置,并将其与它们的异常表达模式相关联。我们使用了几种计算方法,在 ACD11 中发现了 PCD 易感性单核苷酸多态性(SNP)。我们分析了 RNA-Seq 数据,确定了有害的非同义 SNP(nsSNP),构建了遗传突变蛋白结构,并使用分子对接来评估突变的影响。我们的结果表明,GLTP 结构域中的 A15T 和 A39D 突变很可能是极其有害的突变,通过破坏其组成和抑制其催化效率来抑制 ACD11 蛋白结构域的表达。与 A15T 突变体相比,A39D 突变体更有可能破坏蛋白质结构。总之,这些突变体可以帮助更好地理解与 ACD11 基因 GLTP 结构域激活相关的大量 PCD 易感性。