The prefusion structure of the HERV- K (HML-2) Env spike complex

• 成果类型: Article
• 署名作者: Shaked, Ron; Katz, Michael; Dvashi, Hadas Cohen -; Diskin, Ron
• 署名单位: Weizmann Institute of Science
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8944
• DOI: 10.1073/pnas.2505505122
• 发表日期: 2025-07-15
• 关键词: virus; cell; glycoprotein; expression; ELEMENTS; fusion; tm

摘要

The human endogenous retrovirus K (HERV-K) is a retrovirus that got assimilated into the human genome in ancient times and has been inherited in our germline ever since. It enters cells using a class-I spike protein (Env) that mediates receptor recognition and membrane fusion. On top of having a biological role during development, HERV-K is activated in amyotrophic lateral sclerosis, various cancers, and other pathological conditions. Antibodies that target the HERV-K spike complex have therapeutic value, flagging the spike as a novel drug target. Here, we use cryo-EM to determine the trimeric structure of the HERV-K spike. The spike presents a distinct structure, which substantially differs from other class-I fusogens. Nevertheless, some general architectural features suggest a common origin with other retroviruses. The ability to structurally characterize the HERV-K spike may facilitate the development of antibody-based therapies.