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TitleCryo-EM structures of prefusion SIV envelope trimer.
Journal, issue, pagesNat Struct Mol Biol, Vol. 29, Issue 11, Page 1080-1091, Year 2022
Publish dateNov 7, 2022
AuthorsJason Gorman / Chunyan Wang / Rosemarie D Mason / Alexandra F Nazzari / Hugh C Welles / Tongqing Zhou / Julian W Bess / Tatsiana Bylund / Myungjin Lee / Yaroslav Tsybovsky / Raffaello Verardi / Shuishu Wang / Yongping Yang / Baoshan Zhang / Reda Rawi / Brandon F Keele / Jeffrey D Lifson / Jun Liu / Mario Roederer / Peter D Kwong /
PubMed AbstractSimian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. Here we report prefusion ...Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIV) in complex with neutralizing antibodies. These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. We also investigated in situ SIV-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution.
External linksNat Struct Mol Biol / PubMed:36344847 / PubMed Central
MethodsEM (subtomogram averaging) / EM (single particle)
Resolution4.12 - 10.0 Å
Structure data

EMDB-25062: In-situ structure of SIV trimer
Method: EM (subtomogram averaging) / Resolution: 8.5 Å

EMDB-25063: in situ SIVmac239-Env trimers on the surface of AT-2-inactivated virions
Method: EM (subtomogram averaging) / Resolution: 7.0 Å

EMDB-25064: in situ SIVmac239-Env trimers on the surface of AT-2-inactivated virions
Method: EM (subtomogram averaging) / Resolution: 7.0 Å

EMDB-25065: In-situ structure of SIVmac239-Env trimers with ITS90.03 associated
Method: EM (subtomogram averaging) / Resolution: 10.0 Å

EMDB-27631: SIV mac239 SOS-2P K169T Env trimer with bNAb PGT145 and jacalin
Method: EM (single particle) / Resolution: 7.64 Å

EMDB-27718, PDB-8dua:
SIV E660.CR54 SOS-2P Env Trimer with ITS92.02
Method: EM (single particle) / Resolution: 4.32 Å

EMDB-27735, PDB-8dvd:
Cryo-EM structure of SIVmac239 SOS-2P Env trimer in complex with human bNAb PGT145
Method: EM (single particle) / Resolution: 4.12 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-MAN:
alpha-D-mannopyranose / Mannose

Source
  • Simian-Human immunodeficiency virus
  • Artocarpus heterophyllus (jackfruit)
  • Influenza A virus
  • simian immunodeficiency virus
  • macaca mulatta (Rhesus monkey)
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SIV / ITS92 / HIV-1 / quaternary / HIV-2 / VIRAL PROTEIN-IMMUNE SYSTEM complex / CD4 / SOSIP / Vaccine / IMMUNE SYSTEM / VIRAL PROTEIN

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