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A bipartite structural organization defines the SERINC family of HIV-1 restriction factors.
- Source :
-
Nature structural & molecular biology [Nat Struct Mol Biol] 2020 Jan; Vol. 27 (1), pp. 78-83. Date of Electronic Publication: 2020 Jan 06. - Publication Year :
- 2020
-
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.
- Subjects :
- Animals
Drosophila Proteins chemistry
Drosophila Proteins ultrastructure
Drosophila melanogaster chemistry
Humans
Membrane Proteins ultrastructure
Models, Molecular
Protein Conformation
Protein Domains
Protein Multimerization
HIV Infections immunology
HIV-1 immunology
Membrane Proteins chemistry
Membrane Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1545-9985
- Volume :
- 27
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature structural & molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 31907454
- Full Text :
- https://doi.org/10.1038/s41594-019-0357-0