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A bipartite structural organization defines the SERINC family of HIV-1 restriction factors
File | Description | Size | Format | |
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34949_2_merged_1574806756.pdf | Accepted version | 15.73 MB | Adobe PDF | View/Open |
Title: | A bipartite structural organization defines the SERINC family of HIV-1 restriction factors |
Authors: | Pye, VE Rosa, A Bertelli, C Struwe, WB Maslen, SL Corey, R Liko, I Hassall, M Mattiuzzo, G Ballandras-Colas, A Nans, A Takeuchi, Y Stansfeld, PJ Skehel, JM Robinson, CV Pizzato, M Cherepanov, P |
Item Type: | Journal Article |
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. |
Issue Date: | 6-Jan-2020 |
Date of Acceptance: | 26-Nov-2019 |
URI: | http://hdl.handle.net/10044/1/76274 |
DOI: | 10.1038/s41594-019-0357-0 |
ISSN: | 1545-9985 |
Publisher: | Nature Research |
Start Page: | 78 |
End Page: | 83 |
Journal / Book Title: | Nature Structural and Molecular Biology |
Volume: | 27 |
Issue: | 1 |
Copyright Statement: | © 2020 Springer Nature Limited |
Keywords: | 11 Medical and Health Sciences 03 Chemical Sciences 06 Biological Sciences Biophysics Developmental Biology |
Publication Status: | Published |
Conference Place: | United States |
Open Access location: | https://rdcu.be/bZXeZ |
Appears in Collections: | Department of Infectious Diseases |