Pye, VE;
Rosa, A;
Bertelli, C;
Struwe, WB;
Maslen, SL;
Corey, R;
Liko, I;
... Cherepanov, P; + view all
(2020)
A bipartite structural organization defines the SERINC family of HIV-1 restriction factors.
Nature Structural & Molecular Biology
, 27
pp. 78-83.
10.1038/s41594-019-0357-0.
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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.
| Type: | Article |
|---|---|
| Title: | A bipartite structural organization defines the SERINC family of HIV-1 restriction factors |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41594-019-0357-0 |
| Publisher version: | https://doi.org/10.1038/s41594-019-0357-0 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Cryoelectron microscopy, Restriction factors |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10091093 |
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