National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01- AI144022
米国
引用
ジャーナル: Nat Commun / 年: 2021 タイトル: Asymmetrizing an icosahedral virus capsid by hierarchical assembly of subunits with designed asymmetry. 著者: Zhongchao Zhao / Joseph Che-Yen Wang / Mi Zhang / Nicholas A Lyktey / Martin F Jarrold / Stephen C Jacobson / Adam Zlotnick / 要旨: Symmetrical protein complexes are ubiquitous in biology. Many have been re-engineered for chemical and medical applications. Viral capsids and their assembly are frequent platforms for these ...Symmetrical protein complexes are ubiquitous in biology. Many have been re-engineered for chemical and medical applications. Viral capsids and their assembly are frequent platforms for these investigations. A means to create asymmetric capsids may expand applications. Here, starting with homodimeric Hepatitis B Virus capsid protein, we develop a heterodimer, design a hierarchical assembly pathway, and produce asymmetric capsids. In the heterodimer, the two halves have different growth potentials and assemble into hexamers. These preformed hexamers can nucleate co-assembly with other dimers, leading to Janus-like capsids with a small discrete hexamer patch. We can remove the patch specifically and observe asymmetric holey capsids by cryo-EM reconstruction. The resulting hole in the surface can be refilled with fluorescently labeled dimers to regenerate an intact capsid. In this study, we show how an asymmetric subunit can be used to generate an asymmetric particle, creating the potential for a capsid with different surface chemistries.