Program for Nurturing Global Leaders in Tropical Medicine and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Virology. 2019 Jun;532:82-87. doi: 10.1016/j.virol.2019.04.005. Epub 2019 Apr 23.
Cytoplasmic tails of envelope (Env) glycoproteins of many retroviruses inhibit their membrane fusion activity. The cytoplasmic 16-amino acid peptide of ecotropic murine leukemia virus (E-MLV) Env protein, called the R-peptide, also inhibits the membrane fusion activity of the Env protein. However, the molecular mechanism of the inhibition has not been elucidated yet. In this study, we found that R-peptide-containing Env protein of E-MLV binds to the cell surface receptor cationic amino acid transporter-1 (CAT-1) with weaker affinity than R-peptide-truncated Env protein. Consistent with this result, R-peptide-containing Env protein had less efficient inhibition of E-MLV vector infection than R-peptide-truncated Env protein. R-peptide truncation has been reported to induce conformational change in the surface subunit of E-MLV Env protein that interacts with the receptor. Taken together, our findings indicate that R-peptide truncation induces conformational change in the receptor-binding domain of the E-MLV Env protein and facilitates the Env-receptor interaction.
许多逆转录病毒的包膜 (Env) 糖蛋白的细胞质尾部抑制其膜融合活性。嗜性鼠白血病病毒 (E-MLV) Env 蛋白的 16 个氨基酸的细胞质肽，称为 R 肽，也抑制 Env 蛋白的膜融合活性。然而，抑制的分子机制尚未阐明。在这项研究中，我们发现 E-MLV 含 R 肽的 Env 蛋白与细胞表面受体阳离子氨基酸转运蛋白-1 (CAT-1) 的结合亲和力比 R 肽截断的 Env 蛋白弱。与该结果一致，含 R 肽的 Env 蛋白对 E-MLV 载体感染的抑制作用不如 R 肽截断的 Env 蛋白有效。据报道，R 肽截断会诱导与受体相互作用的 E-MLV Env 蛋白表面亚基发生构象变化。综上所述，我们的发现表明，R 肽截断诱导了 E-MLV Env 蛋白的受体结合域的构象变化，并促进了 Env-受体相互作用。
