9SYA

Crystal structure of HERV-K envelope glycoprotein surface subunit with cholates and sulfates bound

Summary for 9SYA

• Entry DOI: 10.2210/pdb9sya/pdb
• Descriptor: Surface protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: envelope protein, viral protein, endogenous retrovirus, betaretrovirus, envelope glycoprotein, n-linked glycosylation, ligand binding site, receptor binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 85551.66

Authors

Nikolopoulos, N.,Modis, Y. (deposition date: 2025-10-10, release date: 2026-04-08, Last modification date: 2026-07-08)

Primary citation

Nikolopoulos, N.,Modis, Y.
Crystal structure of HERV-K envelope glycoprotein surface subunit.
J.Virol., 100:e0019526-e0019526, 2026

PubMed Abstract: 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.

PubMed: 42095673
DOI: 10.1128/jvi.00195-26

Experimental method

X-RAY DIFFRACTION (2.25 Å)