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Nat Struct Mol Biol. 2020 Jan;27(1):78-83. doi: 10.1038/s41594-019-0357-0. Epub 2020 Jan 6.

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

Author information

1
Chromatin Structure and Mobile DNA Laboratory, Francis Crick Institute, London, UK.
2
Department of Cellular, Computational and Integrative Biology, University of Trento, Povo, Italy.
3
Physical and Theoretical Chemistry Laboratory, South Parks Road, Oxford, UK.
4
Biological Mass Spectrometry and Proteomics Laboratory, MRC Laboratory of Molecular Biology, Cambridge, UK.
5
Department of Biochemistry, University of Oxford, Oxford, UK.
6
National Institute for Biological Standards and Control, Hertfordshire, UK.
7
Structural Biology Science Technology Platform, Francis Crick Institute, London, UK.
8
UCL Division of Infection and Immunity, The Rayne Building, London, UK.
9
School of Life Sciences & Department of Chemistry, University of Warwick, Warwick, UK.
10
Department of Cellular, Computational and Integrative Biology, University of Trento, Povo, Italy. massimo.pizzato@unitn.it.
11
Chromatin Structure and Mobile DNA Laboratory, Francis Crick Institute, London, UK. peter.cherepanov@crick.ac.uk.
12
Department of Infectious Disease, Imperial College London, St Mary's Campus, Norfolk Place, London, UK. peter.cherepanov@crick.ac.uk.

Abstract

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.

PMID:
31907454
PMCID:
PMC6956856
[Available on 2020-07-06]
DOI:
10.1038/s41594-019-0357-0

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