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A bipartite structural organization defines the SERINC family of HIV-1 restriction factors.

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posted on 27.08.2020 by Valerie E Pye, Annachiara Rosa, Cinzia Bertelli, Weston B Struwe, Sarah L Maslen, Robin Corey, Idlir Liko, Mark Hassall, Giada Mattiuzzo, Allison Ballandras-Colas, Andrea Nans, Yasuhiro Takeuchi, Phillip J Stansfeld, J Mark Skehel, Carol V Robinson, Massimo Pizzato, Peter Cherepanov
The human integral membrane protein SERINC5 potently restricts HIV-1 infectivity and sensitizes the virus to antibody-mediated neutralization. Here, using cryo-EM, we determine the structures of human SERINC5 and its orthologue from Drosophila melanogaster at subnanometer and near-atomic resolution, respectively. The structures reveal a novel fold comprised of ten transmembrane helices organized into two subdomains and bisected by a long diagonal helix. A lipid binding groove and clusters of conserved residues highlight potential functional sites. A structure-based mutagenesis scan identified surface-exposed regions and the interface between the subdomains of SERINC5 as critical for HIV-1-restriction activity. The same regions are also important for viral sensitization to neutralizing antibodies, directly linking the antiviral activity of SERINC5 with remodeling of the HIV-1 envelope glycoprotein.

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Crick (Grant ID: 10061, Grant title: Cherepanov FC001061)

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