6WXG

Cryo-EM reconstruction of VP5*/VP8* assembly from rhesus rotavirus particles - Reversed conformation

This is a non-PDB format compatible entry.

Summary for 6WXG

• Entry DOI: 10.2210/pdb6wxg/pdb
• EMDB information: 21957
• Descriptor: Outer capsid protein VP4, Intermediate capsid protein VP6, Outer capsid glycoprotein VP7, ... (5 entities in total)
• Functional Keywords: complex, non-enveloped virus, viral particle, entry, membrane-penetration, rotavirus, vp4, vp5*, vp8*, viral protein
• Biological source: Rotavirus A (strain RVA/Monkey/United States/RRV/1975/G3P5B[3]) (RV-A); More
• Total number of polymer chains: 39
• Total formula weight: 1743396.06

Authors

Herrmann, T.,Harrison, S.C.,Jenni, S. (deposition date: 2020-05-10, release date: 2021-01-20, Last modification date: 2021-03-10)

Primary citation

Herrmann, T.,Torres, R.,Salgado, E.N.,Berciu, C.,Stoddard, D.,Nicastro, D.,Jenni, S.,Harrison, S.C.
Functional refolding of the penetration protein on a non-enveloped virus.
Nature, 590:666-670, 2021

PubMed Abstract: A non-enveloped virus requires a membrane lesion to deliver its genome into a target cell. For rotaviruses, membrane perforation is a principal function of the viral outer-layer protein, VP4. Here we describe the use of electron cryomicroscopy to determine how VP4 performs this function and show that when activated by cleavage to VP8* and VP5*, VP4 can rearrange on the virion surface from an 'upright' to a 'reversed' conformation. The reversed structure projects a previously buried 'foot' domain outwards into the membrane of the host cell to which the virion has attached. Electron cryotomograms of virus particles entering cells are consistent with this picture. Using a disulfide mutant of VP4, we have also stabilized a probable intermediate in the transition between the two conformations. Our results define molecular mechanisms for the first steps of the penetration of rotaviruses into the membranes of target cells and suggest similarities with mechanisms postulated for other viruses.

PubMed: 33442061
DOI: 10.1038/s41586-020-03124-4

Experimental method

ELECTRON MICROSCOPY (3.3 Å)