细胞LxxLL基因被乳头瘤病毒E6上蛋白劫持的结构基础
Katia Zanier1, Sebastian Charbonnier, Abdellahi Ould M'hamed Ould Sidi
1Biotechnologie et Signalisation Cellulaire UMR 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, BP 10413, F-67412 Illkirch, France.
概括
乳头瘤病毒E6coproteins通过LxxLL基因与宿主蛋白结合,驱动上皮瘤. 结构分析显示,对于E6的致癌活性和多功能性至关重要的一种保存口袋.
科学领域:
- 结构生物学是结构生物学.
- 病毒学 病毒学
- 癌症研究 癌症研究
背景情况:
- 在乳头瘤病毒诱导的上皮细胞瘤中,如人类宫癌中,E6病毒瘤蛋白非常重要.
- E6蛋白通过特定的酸性LxxLL基因与宿主蛋白相互作用.
研究的目的:
- 阐明E6蛋白与LxxLL基因相互作用的结构基础.
- 了解LxxLL结合口袋在E6致癌活性和多功能性中的作用.
主要方法:
- 使用X射线晶体学来确定与LxxLL结合的牛乳头瘤病毒E6 (BPV1) 和人类乳头瘤病毒E6 (HPV16) 的结构.
- 结构分析的重点是E6域,链接螺旋和螺旋式LxxLL图案之间的相互作用.
主要成果:
- 晶体结构显示,BPV1和HPV16 E6蛋白质都具有由域和链接螺旋组成的基本疏水口袋.
- 这个口袋可以容纳螺旋式LxxLL图案,暗示了保存的结合机制.
- 这口袋的突变性无活化取消了这两种E6蛋白的致癌活性.
结论:
- 这项研究揭示了乳头瘤病毒E6蛋白质的多功能性和瘤性结构基础.
- 已识别的LxxLL结合口袋对于E6在瘤发育中的作用至关重要.
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