对ZAP及其辅因子的进化分析确定了内在无序的区域作为宿主-病原体相互作用的中心元素
Rachele Cagliani1, Diego Forni1, Alessandra Mozzi1
1Scientific Institute IRCCS E. MEDEA, Computational Biology Unit, Bosisio Parini 23842, Italy.
Computational and structural biotechnology journal
|September 5, 2024
概括
指抗病毒蛋白 (ZAP) 和其辅因子由于宿主-病原体冲突而迅速演变. 这些蛋白质内的内在无序区域 (IDR) 是这种进化的关键驱动因素,可能通过相分离影响抗病毒功能.
科学领域:
- 进化生物学是进化的生物学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 指抗病毒蛋白 (ZAP) 对于天生的免疫非常重要,它能感知外来核酸.
- 扎普与TRIM25,Riplet和KHNYN等辅因子相互作用,产生抗病毒活性.
- 与病原体相互作用的蛋白质通常由于遗传冲突而经历快速演变.
研究的目的:
- 研究ZAP的进化历史及其哺乳动物中的辅因子.
- 确定积极选择的地区及其功能意义.
- 探索内在无序区域 (IDR) 在抗病毒蛋白的进化中的作用.
主要方法:
- 在四个哺乳动物群体中对ZAP和辅助因子进行了in silico分子进化分析.
- 确定积极选择的地点,并分析进化速率.
- IDRs的生物物理性质分析,包括链条紧缩和形态.
- 阶段分离 (PS) 促进区域的预测.
主要成果:
- 在大多数哺乳动物群体中,ZAP及其辅因子中发现了积极选择的证据.
- 本质上无序的区域 (IDRs) 的发展速度明显快于折叠的域,并且包含了大多数选定的网站.
- 在ZAP中PARP域显示了选择,表明ADP-核糖酶结合的调制.
- 在ZAP和KHNYN的IDR是紧的,并促进相分离 (PS),在这些地区有大量的选定的地点.
结论:
- IDRs对于ZAP及其在宿主-病原体相互作用中的辅因子的演变至关重要.
- 阶段分离 (PS) 可能是这些蛋白质抗病毒功能的关键机制.
- ZAP和辅助因子的快速演变反映了与病毒进行的进化军备竞赛.
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