Department of Biophysics, University of Delhi South Campus, New Delhi, India.
PLoS One. 2022 Apr 14;17(4):e0265657. doi: 10.1371/journal.pone.0265657. eCollection 2022.
Microbial mimicry of the host proteins/peptides can elicit host auto-reactive T- or B-cells resulting in autoimmune disease(s). Since intrinsically disordered protein regions (IDPRs) are involved in several host cell signaling and PPI networks, molecular mimicry of the IDPRs can help the pathogens in substituting their own proteins in the host cell-signaling and PPI networks and, ultimately hijacking the host cellular machinery. Thus, the present study was conducted to discern the structural disorder and intrinsically disordered protein regions (IDPRs) like, molecular recognition features (MoRFs), short linear motifs (SLiMs), and low complexity regions (LCRs) in the experimentally verified mimicry proteins and peptides (mimitopes) of bacteria, viruses and host. Also, functional characteristics of the mimicry proteins were studied in silico. Our results indicated that 78% of the bacterial host mimicry proteins and 45% of the bacterial host mimitopes were moderately/highly disordered while, 73% of the viral host mimicry proteins and 31% of the viral host mimitopes were moderately/highly disordered. Among the pathogens, 27% of the bacterial mimicry proteins and 13% of the bacterial mimitopes were moderately/highly disordered while, 53% of the viral mimicry proteins and 21% of the viral mimitopes were moderately/highly disordered. Though IDPR were frequent in host, bacterial and viral mimicry proteins, only a few mimitopes overlapped with the IDPRs like, MoRFs, SLiMs and LCRs. This suggests that most of the microbes cannot use molecular mimicry to modulate the host PPIs and hijack the host cell machinery. Functional analyses indicated that most of the pathogens exhibited mimicry with the host proteins involved in ion binding and signaling pathways. This is the first report on the disordered regions and functional aspects of experimentally proven host and microbial mimicry proteins.
宿主蛋白/肽的微生物模拟可以引发宿主自身反应性 T 或 B 细胞，从而导致自身免疫性疾病。由于无规卷曲蛋白区域（IDPR）参与了几个宿主细胞信号和蛋白质-蛋白质相互作用网络，因此 IDPR 的分子模拟可以帮助病原体在宿主细胞信号和蛋白质-蛋白质相互作用网络中替代自身蛋白，并最终劫持宿主细胞机制。因此，本研究旨在辨别细菌、病毒和宿主中经过实验验证的模拟蛋白和肽（模拟肽）中的结构无序和无规卷曲蛋白区域（IDPR），如分子识别特征（MoRFs）、短线性基序（SLiMs）和低复杂度区域（LCRs）。此外，还在计算机上研究了模拟蛋白的功能特征。我们的结果表明，78%的细菌宿主模拟蛋白和 45%的细菌宿主模拟肽中度/高度无序，而 73%的病毒宿主模拟蛋白和 31%的病毒宿主模拟肽中度/高度无序。在病原体中，27%的细菌模拟蛋白和 13%的细菌模拟肽中度/高度无序，而 53%的病毒模拟蛋白和 21%的病毒模拟肽中度/高度无序。虽然 IDPR 在宿主、细菌和病毒模拟蛋白中很常见，但只有少数模拟肽与 IDPR 重叠，如 MoRFs、SLiMs 和 LCRs。这表明大多数微生物不能利用分子模拟来调节宿主蛋白质-蛋白质相互作用并劫持宿主细胞机制。功能分析表明，大多数病原体与宿主蛋白模拟涉及离子结合和信号通路。这是关于经过实验验证的宿主和微生物模拟蛋白的无序区域和功能方面的第一份报告。
