Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu

Biochemistry. 2024 Feb 6;63(3):241-250. doi: 10.1021/acs.biochem.3c00437. Epub 2024 Jan 12.

Abstract

Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for the mechanisms of their biological functions as well as their potential as therapeutic targets.

MeSH terms

  • COVID-19*
  • HIV Infections*
  • Human Immunodeficiency Virus Proteins / chemistry
  • Human Immunodeficiency Virus Proteins / metabolism
  • Humans
  • Poliovirus*
  • SARS-CoV-2 / metabolism
  • Viral Regulatory and Accessory Proteins
  • Viroporin Proteins

Substances

  • Viroporin Proteins
  • Viral Regulatory and Accessory Proteins
  • Human Immunodeficiency Virus Proteins