Structural basis for tetherin antagonism as a barrier to zoonotic lentiviral transmission
Copyright policy )Structural basis for tetherin antagonism as a barrier to zoonotic lentiviral transmission
AbstractTetherin is a host defense that physically prevents escape of virions from the plasma membrane. Human tetherin lacks the motif DIWK antagonized by SIV, the antecedent of HIV. Here, we reconstituted the AP-2 clathrin adaptor complex with a simian tetherin and SIV Nef and determined its structure by cryo-EM. Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of MHC-I, CD3, and CD4, but overlaps the site for SERINC5 restricting viral infectivity. The structure explains the dependence of SIVs on the host tetherin DIWK sequence and the consequent barrier to human transmission.
- University of California System United States
- Ulm University Medical Center Germany
- Lawrence Berkeley National Laboratory United States
- University of Ulm Germany
- UNIVERSITY OF CALIFORNIA BERKELEY
Models, Molecular, Protein Folding, nef, CD3 Complex, Protein Conformation, Simian Acquired Immunodeficiency Syndrome, Gene Products, nef, host-factor restriction, Models, Zoonoses, 2.2 Factors relating to the physical environment, Aetiology, Bone Marrow Stromal Antigen 2, Simian immunodeficiency virus, tetherin, Biological Sciences, Medical microbiology, hydrogen-deuterium exchange, Infectious Diseases, SIV, Medical Microbiology, CD4 Antigens, HIV/AIDS, Simian Immunodeficiency Virus, Infection, 1.1 Normal biological development and functioning, Immunology, Primary Cell Culture, Adaptor Protein Complex 2, 610, Down-Regulation, Microbiology, clathrin, trafficking, Gene Products, Animals, Humans, Protein Interaction Domains and Motifs, Adaptor Protein Complex beta Subunits, Binding Sites, Biomedical and Clinical Sciences, alpha-Helical, Cell Membrane, Cryoelectron Microscopy, Histocompatibility Antigens Class I, Virion, Molecular, HIV, Membrane Proteins, HEK293 Cells, Biochemistry and cell biology, Lentivirus Infections, Sexually Transmitted Infections, cryo-EM, Biochemistry and Cell Biology, Sequence Alignment, adaptor protein, Antimicrobial Cationic Peptides
Models, Molecular, Protein Folding, nef, CD3 Complex, Protein Conformation, Simian Acquired Immunodeficiency Syndrome, Gene Products, nef, host-factor restriction, Models, Zoonoses, 2.2 Factors relating to the physical environment, Aetiology, Bone Marrow Stromal Antigen 2, Simian immunodeficiency virus, tetherin, Biological Sciences, Medical microbiology, hydrogen-deuterium exchange, Infectious Diseases, SIV, Medical Microbiology, CD4 Antigens, HIV/AIDS, Simian Immunodeficiency Virus, Infection, 1.1 Normal biological development and functioning, Immunology, Primary Cell Culture, Adaptor Protein Complex 2, 610, Down-Regulation, Microbiology, clathrin, trafficking, Gene Products, Animals, Humans, Protein Interaction Domains and Motifs, Adaptor Protein Complex beta Subunits, Binding Sites, Biomedical and Clinical Sciences, alpha-Helical, Cell Membrane, Cryoelectron Microscopy, Histocompatibility Antigens Class I, Virion, Molecular, HIV, Membrane Proteins, HEK293 Cells, Biochemistry and cell biology, Lentivirus Infections, Sexually Transmitted Infections, cryo-EM, Biochemistry and Cell Biology, Sequence Alignment, adaptor protein, Antimicrobial Cationic Peptides
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