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-Structure paper
Title | Human paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery. |
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Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 121, Issue 11, Page e2307812120, Year 2024 |
Publish date | Mar 12, 2024 |
Authors | Victoria Madigan / Yugang Zhang / Rumya Raghavan / Max E Wilkinson / Guilhem Faure / Elena Puccio / Michael Segel / Blake Lash / Rhiannon K Macrae / Feng Zhang / |
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 - ...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. |
External links | Proc Natl Acad Sci U S A / PubMed:38437549 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.09 - 3.3 Å |
Structure data | EMDB-42812: PNMA2 capsid, overall icosahedral map EMDB-42815: PNMA2 capsid, focussed refinement of a pentamer (C5 symmetry) |
Source |
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Keywords | VIRUS LIKE PARTICLE / capsid / endogenous retrovirus-like particle / paraneoplasm / antigen |