Crystal structure of HERV-K envelope glycoprotein surface subunit

Area of Science:

• Structural Biology
• Virology
• Genomics

Background:

• Human endogenous retroviruses (HERVs) comprise 8-15% of the human genome.
• The HERV-K family is transcriptionally active and can proliferate, expressing viral proteins.
• Aberrant HERV-K envelope glycoprotein (Env) expression is linked to cancer, neurodegeneration, and autoimmune diseases.

Purpose of the Study:

• To determine the crystal structure of the HERV-K HML-2 Env surface subunit (SU).
• To provide an atomic-level understanding of HERV-K Env structure for future research.

Main Methods:

• X-ray crystallography was used to determine the structure.
• The resolution of the crystal structure was 2.25 Å.

Main Results:

• The HERV-K HML-2 Env SU structure reveals similarities to Syncytin-2 SU and HIV-1 gp120.
• The structure features five disulfide bonds, four N-linked glycans, two sulfate ions, and three steroid molecules.
• Identified potential interaction surfaces for cellular receptors and binding sites for small molecules.

Conclusions:

• The crystal structure offers a foundation for mapping autoantigenic epitopes.
• It facilitates the identification of small molecules to inhibit HERV-K activity.
• Enhances mechanistic understanding of retroviral structures and functions.