9MLA

Pre-fusion HERV-K Envelope Protein Trimer Ectodomain in complex with Kenv-6 Fab

9MLA の概要

• エントリーDOI: 10.2210/pdb9mla/pdb
• 関連するPDBエントリー: 9MLK 9O4F
• EMDBエントリー: 48351
• 分子名称: Surface protein, Transmembrane protein,Fibritin, Kenv-6 Fab heavy chain, ... (9 entities in total)
• 機能のキーワード: human endogenous retrovirus k, glycoprotein, herv-k, envelope, pre-fusion, fab complex, viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 299143.48

構造登録者

Shek, J.,Sun, C.,Hastie, K.,Saphire, E.O. (登録日: 2024-12-18, 公開日: 2025-07-30, 最終更新日: 2025-09-03)

主引用文献

Shek, J.,Sun, C.,Wilson, E.M.,Moadab, F.,Hastie, K.M.,Rajamanickam, R.R.,Penalosa, P.J.,Harkins, S.S.,Parekh, D.,Hariharan, C.,Zyla, D.S.,Yu, C.,Shaffer, K.C.L.,Lewis, V.I.,Avalos, R.D.,Mustelin, T.,Saphire, E.O.
Human endogenous retrovirus K (HERV-K) envelope structures in pre- and postfusion by cryo-EM.
Sci Adv, 11:eady8168-eady8168, 2025

PubMed Abstract: Human endogenous retroviruses (HERVs) are remnants of ancient infections that comprise ~8% of the human genome. The HERV-K envelope glycoprotein (Env) is aberrantly expressed in cancers, autoimmune disorders, and neurodegenerative diseases, and is targeted by patients' own antibodies. However, a lack of structural information has limited molecular and immunological studies of the roles of HERVs in disease. Here, we present cryo-electron microscopy structures of stabilized HERV-K Env in the prefusion conformation, revealing a distinct fold and architecture compared to HIV and simian immunodeficiency virus. We also generated and characterized a panel of monoclonal antibodies with subunit and conformational specificity, serving as valuable research tools. These antibodies enabled structure determination of the postfusion conformation of HERV-K Env, including its unique "tether" helix, and antibody-bound prefusion Env. Together, these results provide a structural framework that opens the door to mechanistic studies of HERV-K Env and tools for its evaluation as a potential therapeutic target.

PubMed: 40864726
DOI: 10.1126/sciadv.ady8168

実験手法

ELECTRON MICROSCOPY (2.24 Å)