Pye, V.E., Rosa, A., Bertelli, C., Struwe, W.B., Maslen, S.L., Corey, R., Liko, I., Hassall, M., Mattiuzzo, G., Ballandras-Colas, A., Nans, A., Takeuchi, Y., Stansfeld, P.J., Skehel, J.M., Robinson, C.V., Pizzato, M., Cherepanov, P. (2020). A bipartite structural organization defines the SERINC family of HIV-1 restriction factors.  Nat. Struct. Mol. Biol. 27(1): 78--83.

FBrf0244518

Research paper

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.

PMC6956856 (PMC) (EuropePMC)