人体内源逆转录病毒包膜HEMO蛋白与BACE2相互作用:在灵长类动物血统中获得的新型伙伴关系
Anthony Béguin1, Marianne Chasseriaud1, Guillaume Hollaender1
1Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, CNRS UMR 9196, Gustave Roussy, Université Paris-Saclay, Villejuif 94805, France.
概括
像HEMO这样的人类内源逆转录病毒 (HERV) 已经进化. 研究人员发现,HEMO蛋白与BACE2蛋白酶相互作用,这表明HERVs具有新的生理作用.
科学领域:
- 基因组学就是基因组学.
- 进化生物学 进化生物学
- 病毒学 病毒学
背景情况:
- 内生逆转录病毒 (ERV) 占哺乳动物基因组的很大一部分.
- 一些ERV基因,如syncytins,已经被抽取,这有助于哺乳动物的进化,特别是胎盘哺乳动物.
- 最古老的全长逆转录病毒包膜基因,人类内生MER34ORF (HEMO),在人类基因组中被确定,起源于1亿年前.
研究的目的:
- 为了确定人类内源MER34 ORF (HEMO) 蛋白质的受体或相互作用伙伴.
- 研究HEMO-BACE2相互作用的进化出现和潜在的生理功能.
主要方法:
- 利用使用麻疹病毒蛋白质的细胞细胞融合查策略,从人类ORFeome库中识别HEMO相互作用体.
- 在祖先哺乳动物HEMO序列的重建中使用,以确定相互作用的进化时间.
主要成果:
- 确定BACE2 (β-site APP-cleaving enzyme 2) 作为可溶性 (SHED) 和跨膜HEMO蛋白的特定相互作用伙伴.
- 确定HEMO-BACE2相互作用在3000万到450万年前的猿类白血统中出现,与HEMO的特定突变相吻合.
- 这些突变导致了氨酸裂变的丧失,并使其与BACE2相互作用,可能延长HEMO的保存时间.
结论:
- BACE2是内源性逆转录病毒蛋白HEMO的特定结合伙伴.
- 灵长类动物中HEMO-BACE2相互作用的演化表明,HEMO在基因组中维持了数百万年的保存生理作用.
- 这种相互作用可能代表了内源性逆转录病毒基因的新型捕获事件.
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