Scholarlink

<p>Human immunodeficiency virus-1 (HIV-1) remains a global health crisis, with over 40 million people living with the virus and no effective vaccine available. Central to HIV infection and immune evasion is the envelope glycoprotein (Env), a heavily glycosylated class I fusion protein that mediates viral entry and is the sole immunogenic target. Despite the recent advancements provided by imaging techniques, the characterization of Env’s structure and dynamics within its native membrane environment remains incomplete. Here, we present microsecond-long, all-atom molecular dynamics simulations of the full-length, glycosylated Env glycoprotein embedded in a biologically relevant lipid bilayer. Our simulations, corroborated by cryo-electron tomography, reveal a pronounced tilting motion of Env relative to the membrane. Importantly, we identify a critical role for N-linked glycans at N88 and N611 in modulating the transition to tilted conformations. Alongside illuminating the sites of vulnerability within the glycan shield, the results presented here underscore Env tilting dynamics as a feature that can be leveraged in immunogen design.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

N-Glycans modulate tilting of HIV-1 envelope glycoprotein

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月15日

查看全文
  • Mohamed Shehata,
  • Lorenzo Casalino,
  • Madeleine Duquette,
  • Siyu Chen,
  • Alex Flaherty,
  • Patrick M. Waller,
  • Elizabeth Villa,
  • Rommie E. Amaro

摘要

Human immunodeficiency virus-1 (HIV-1) remains a global health crisis, with over 40 million people living with the virus and no effective vaccine available. Central to HIV infection and immune evasion is the envelope glycoprotein (Env), a heavily glycosylated class I fusion protein that mediates viral entry and is the sole immunogenic target. Despite the recent advancements provided by imaging techniques, the characterization of Env’s structure and dynamics within its native membrane environment remains incomplete. Here, we present microsecond-long, all-atom molecular dynamics simulations of the full-length, glycosylated Env glycoprotein embedded in a biologically relevant lipid bilayer. Our simulations, corroborated by cryo-electron tomography, reveal a pronounced tilting motion of Env relative to the membrane. Importantly, we identify a critical role for N-linked glycans at N88 and N611 in modulating the transition to tilted conformations. Alongside illuminating the sites of vulnerability within the glycan shield, the results presented here underscore Env tilting dynamics as a feature that can be leveraged in immunogen design.