8UYO

Structure of a recombinant human PNMA2 capsid

8UYO の概要

• エントリーDOI: 10.2210/pdb8uyo/pdb
• EMDBエントリー: 42812
• 分子名称: Paraneoplastic antigen Ma2 (1 entity in total)
• 機能のキーワード: capsid, endogenous retrovirus-like particle, paraneoplasm, antigen, virus like particle
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41557.29

構造登録者

Wilkinson, M.E.,Madigan, V.,Zhang, Y.,Zhang, F. (登録日: 2023-11-13, 公開日: 2024-03-20)

主引用文献

Madigan, V.,Zhang, Y.,Raghavan, R.,Wilkinson, M.E.,Faure, G.,Puccio, E.,Segel, M.,Lash, B.,Macrae, R.K.,Zhang, F.
Human paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery.
Proc.Natl.Acad.Sci.USA, 121:e2307812120-e2307812120, 2024

PubMed Abstract: A number of endogenous genes in the human genome encode retroviral -like proteins, which were domesticated from ancient retroelements. The paraneoplastic Ma antigen (PNMA) family members encode a -like capsid domain, but their ability to assemble as capsids and traffic between cells remains mostly uncharacterized. Here, we systematically investigate human PNMA proteins and find that a number of PNMAs are secreted by human cells. We determine that PNMA2 forms icosahedral capsids efficiently but does not naturally encapsidate nucleic acids. We resolve the cryoelectron microscopy (cryo-EM) structure of PNMA2 and leverage the structure to design engineered PNMA2 (ePNMA2) particles with RNA packaging abilities. Recombinantly purified ePNMA2 proteins package mRNA molecules into icosahedral capsids and can function as delivery vehicles in mammalian cell lines, demonstrating the potential for engineered endogenous capsids as a nucleic acid therapy delivery modality.

PubMed: 38437549
DOI: 10.1073/pnas.2307812120

実験手法

ELECTRON MICROSCOPY (3.3 Å)