8RB4

Structure of the five-fold capsomer of the PNMA2 capsid

8RB4 の概要

• エントリーDOI: 10.2210/pdb8rb4/pdb
• EMDBエントリー: 19025
• 分子名称: Paraneoplastic antigen Ma2 homolog (1 entity in total)
• 機能のキーワード: endogenous retrovirus. pnma2, pnma, paraneoplastic syndrome, paraneoplastic antigen ma2, vlp., virus like particle
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 103338.95

構造登録者

Erlendsson, S.,Xu, J.,Shepherd, J.D.,Briggs, J.A.G. (登録日: 2023-12-02, 公開日: 2024-02-14, 最終更新日: 2024-02-28)

主引用文献

Xu, J.,Erlendsson, S.,Singh, M.,Holling, G.A.,Regier, M.,Ibiricu, I.,Einstein, J.,Hantak, M.P.,Day, G.S.,Piquet, A.L.,Smith, T.L.,Clardy, S.L.,Whiteley, A.M.,Feschotte, C.,Briggs, J.A.G.,Shepherd, J.D.
PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome.
Cell, 187:831-, 2024

PubMed Abstract: 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.

PubMed: 38301645
DOI: 10.1016/j.cell.2024.01.009

実験手法

ELECTRON MICROSCOPY (3.2 Å)