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TitleThe prefusion structure of the HERV-K (HML-2) Env spike complex.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 122, Issue 28, Page e2505505122, Year 2025
Publish dateJul 15, 2025
AuthorsRon Shaked / Michael Katz / Hadas Cohen-Dvashi / Ron Diskin /
PubMed AbstractThe 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- ...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.
External linksProc Natl Acad Sci U S A / PubMed:40632556 / PubMed Central
MethodsEM (single particle)
Resolution2.13 Å
Structure data

49572

9nnd

EMDB-49572, PDB-9nnd:
Structure of the HERV-K (HML-2) spike complex
Method: EM (single particle) / Resolution: 2.13 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / HERV-K Endogenous retrovirus K Spike protein Viral glycoprotein / HML-2

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