9NND

Structure of the HERV-K (HML-2) spike complex

Summary for 9NND

• Entry DOI: 10.2210/pdb9nnd/pdb
• EMDB information: 49572
• Descriptor: Endogenous retrovirus group K member 7 Pol protein, Surface protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: herv-k endogenous retrovirus k spike protein viral glycoprotein, viral protein, hml-2
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 223516.92

Authors

Shaked, R.,Katz, M.,Diskin, R. (deposition date: 2025-03-05, release date: 2025-07-02, Last modification date: 2025-07-16)

Primary citation

Shaked, R.,Katz, M.,Cohen-Dvashi, H.,Diskin, R.
The prefusion structure of the HERV-K (HML-2) Env spike complex.
Proc.Natl.Acad.Sci.USA, 122:e2505505122-e2505505122, 2025

PubMed Abstract: 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.

PubMed: 40632556
DOI: 10.1073/pnas.2505505122

Experimental method

ELECTRON MICROSCOPY (2.13 Å)