Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autonóma de Guerrero, Chilpancingo, CP 39087, Mexico.
Laboratorio de Bioinformática y Simulación Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán Sinaloa, CP 80030, Mexico.
Int J Mol Sci. 2021 Jan 30;22(3):1400. doi: 10.3390/ijms22031400.
The oncogenic potential of high-risk human papillomavirus (HPV) is predicated on the production of the E6 and E7 oncoproteins, which are responsible for disrupting the control of the cell cycle. Epidemiological studies have proposed that the presence of the N29S and H51N variants of the HPV16 E7 protein is significantly associated with cervical cancer. It has been suggested that changes in the amino acid sequence of E7 variants may affect the oncoprotein 3D structure; however, this remains uncertain. An analysis of the structural differences of the HPV16 E7 protein and its variants (N29S and H51N) was performed through homology modeling and structural refinement by molecular dynamics simulation. We propose, for the first time, a 3D structure of the E7 reference protein and two of Its variants (N29S and H51N), and conclude that the mutations induced by the variants in N29S and H51N have a significant influence on the 3D structure of the E7 protein of HPV16, which could be related to the oncogenic capacity of this protein.
高危型人乳头瘤病毒（HPV）的致癌潜能取决于 E6 和 E7 癌蛋白的产生，这两种蛋白负责破坏细胞周期的控制。流行病学研究表明，HPV16 E7 蛋白的 N29S 和 H51N 变体的存在与宫颈癌显著相关。有人提出，E7 变体的氨基酸序列变化可能会影响癌蛋白的 3D 结构；然而，这一点仍不确定。通过同源建模和分子动力学模拟的结构细化，对 HPV16 E7 蛋白及其变体（N29S 和 H51N）的结构差异进行了分析。我们首次提出了 E7 参考蛋白及其两种变体（N29S 和 H51N）的 3D 结构，并得出结论，N29S 和 H51N 变体引起的突变对 HPV16 的 E7 蛋白的 3D 结构有显著影响，这可能与该蛋白的致癌能力有关。
