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TitlePNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome.
Journal, issue, pagesCell, Vol. 187, Issue 4, Page 831-845.e19, Year 2024
Publish dateFeb 15, 2024
AuthorsJunjie Xu / Simon Erlendsson / Manvendra Singh / G Aaron Holling / Matthew Regier / Iosune Ibiricu / Jenifer Einstein / Michael P Hantak / Gregory S Day / Amanda L Piquet / Tammy L Smith / Stacey L Clardy / Alexandra M Whiteley / Cédric Feschotte / John A G Briggs / Jason D Shepherd /
PubMed AbstractThe paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are ...The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.
External linksCell / PubMed:38301645 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.3 Å
Structure data

19024

8rb3

EMDB-19024, PDB-8rb3:
Structure of the PNMA2 capsid
Method: EM (single particle) / Resolution: 3.2 Å

19025

8rb4

EMDB-19025, PDB-8rb4:
Structure of the five-fold capsomer of the PNMA2 capsid
Method: EM (single particle) / Resolution: 3.2 Å

19026

8rb5

EMDB-19026, PDB-8rb5:
Structure of the three-fold capsomer of the PNMA2 capsid
Method: EM (single particle) / Resolution: 3.3 Å

19027

8rb7

EMDB-19027, PDB-8rb7:
Structure of the two-fold capsomer of the PNMA2 capsid
Method: EM (single particle) / Resolution: 3.2 Å

Source
  • mus musculus (house mouse)
KeywordsVIRUS LIKE PARTICLE / Endogenous retrovirus. PNMA2 / PNMA / Paraneoplastic syndrome / Paraneoplastic antigen Ma2 / VLP.

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