8UYO

Structure of a recombinant human PNMA2 capsid

Summary for 8UYO

• Entry DOI: 10.2210/pdb8uyo/pdb
• EMDB information: 42812
• Descriptor: Paraneoplastic antigen Ma2 (1 entity in total)
• Functional Keywords: capsid, endogenous retrovirus-like particle, paraneoplasm, antigen, virus like particle
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 41557.29

Authors

Wilkinson, M.E.,Madigan, V.,Zhang, Y.,Zhang, F. (deposition date: 2023-11-13, release date: 2024-03-20)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.3 Å)