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April 11th, 2025
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King\\\'s College London
biophysics
biorxiv

Alpha-BET: Functional labeling of envelope glycoproteins with single domain antibodies for in-virus single molecule imaging

Williamson, D. J.Open in Google Scholar•Zaza, C.Open in Google Scholar•Carlon Andres, I.Open in Google Scholar•Gentili, A.Open in Google Scholar•Daly, J. I.Open in Google Scholar•Holmes, H.Open in Google Scholar•Thrush, J.Open in Google Scholar•Starling, T.Open in Google Scholar•Neil, S.Open in Google Scholar•Owens, R.Open in Google Scholaret al.

We present Alpha-BET, a structure-guided strategy leveraging AlphaFold to identify optimal ALFAtag insertion sites for minimally disruptive labeling of viral glycoproteins with high-affinity nanobodies. Applied to HIV-1 Env, SARS-CoV-2 S, and Nipah G, Alpha-BET preserves structural integrity and function. For HIV-1 Env, we demonstrate super-resolution DNA-PAINT MINFLUX 3D imaging enabled by tag insertion, showcasing its power for visualizing native trimers in single virions and potential for broader virological applications.

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