Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, United States.
New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, New York 10027, United States.
Biochemistry. 2024 Feb 6;63(3):241-250. doi: 10.1021/acs.biochem.3c00437. Epub 2024 Jan 12.
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.
病毒孔道蛋白是一类具有多种功能的病毒膜蛋白，在病毒生命周期中发挥着重要作用。它们可以自我组装并在双层膜中形成孔道，运输对病毒感染周期至关重要的底物，如离子和遗传物质。然而，大多数病毒孔道蛋白的寡聚状态知之甚少。在这里，我们使用胶束中的 native mass spectrometry 来揭示全长 SARS-CoV-2 包膜 (E) 蛋白、脊髓灰质炎病毒 VP4 和 HIV Vpu 的聚合状态。我们的数据表明，E 蛋白是一种特异性二聚体，VP4 完全是单体，而 Vpu 在这些条件下组装成多分散的寡聚物混合物。总的来说，这些结果揭示了病毒孔道蛋白聚合状态的多样性，这对它们的生物学功能机制以及作为治疗靶点的潜力都有影响。
