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

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Pye, Valerie | Rosa, Annachiara | Bertelli, Cinzia | Struwe, Weston | Maslen, Sarah | Corey, Robin | Liko, Idlir | Hassall, Mark | Mattiuzzo, Giada | Ballandras-Colas, Allison | Nans, Andrea | Takeuchi, Yasuhiro | Stansfeld, Phillip | Skehel, J. Mark | Robinson, Carol | Pizzato, Massimo | Cherepanov, Peter

Edité par CCSD ; Nature Publishing Group -

International audience. 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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