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

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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