| Title: |
Crystal structure of HERV-K envelope glycoprotein surface subunit. |
| Authors: |
Nikolopoulos, Nikos; Modis, Yorgo |
| Publisher Information: |
American Society for Microbiology; Department of Medicine; //doi.org/10.1128/jvi.00195-26 |
| Publication Year: |
2026 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
N-linked glycosylation; X-ray crystallography; betaretrovirus; endogenous retrovirus; envelope glycoprotein; ligand binding site; receptor-binding protein; Endogenous Retroviruses; Crystallography; X-Ray; Models; Molecular; Viral Envelope Proteins; Humans; Protein Conformation; Gene Products; env |
| Description: |
The most recently acquired and transcriptionally active family of human endogenous retroviruses (HERVs) is HERV-K. Of the approximately 100 copies of HERV-K in our genome, many retain the potential to proliferate by retrotransposition, express viral proteins, and form functional virus particles. Aberrant expression of the HERV-K envelope glycoprotein (Env) has been associated with cancer and neurodegeneration. Autoantibodies against HERV-K Env have been found in patients with various autoimmune diseases. Here, we report the crystal structure of the Env surface subunit (SU) from HERV-K HML-2, determined at 2.25-Å resolution. The overall fold is somewhat similar to Syncytin-2 SU and distantly related to HIV-1 gp120. The structure contains five disulfides, four N-linked glycans, and two sulfate ions bound to a basic surface groove. Two extended loops form a surface for potential interactions with cell-surface receptors or other cellular factors. The structure also contains three steroid molecules bound to hydrophobic surface patches. This crystal structure provides a platform for future studies to map autoantigenic epitopes, identify small molecules that interfere with HERV-K activity, and extend our mechanistic understanding of retroviruses.IMPORTANCEEight percent to 15% of the human genome consists of endogenous retroviruses and other virus-derived elements inherited from ancestral viral infections. Many endogenous retroviruses from the HERV-K family retain the ability to proliferate across the genome and produce virus-like particles. Aberrant expression of the HERV-K envelope glycoprotein is associated with cancer, neurodegeneration, and autoimmune disease. Here, we report the crystal structure of the HERV-K envelope glycoprotein surface subunit. The structure provides an atomic-level view of the molecular components in HERV-K most likely to trigger autoimmune responses and identifies potential binding sites for drug-like molecules and cell-surface polysaccharides. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/401330; https://doi.org/10.17863/CAM.129202 |
| DOI: |
10.17863/CAM.129202 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/401330; https://doi.org/10.17863/CAM.129202 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.57EB032E |
| Database: |
BASE |