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TitleCryo-ET of Env on intact HIV virions reveals structural variation and positioning on the Gag lattice.
Journal, issue, pagesCell, Vol. 185, Issue 4, Page 641-653.e17, Year 2022
Publish dateFeb 17, 2022
AuthorsVidya Mangala Prasad / Daniel P Leaman / Klaus N Lovendahl / Jacob T Croft / Mark A Benhaim / Edgar A Hodge / Michael B Zwick / Kelly K Lee /
PubMed AbstractHIV-1 Env mediates viral entry into host cells and is the sole target for neutralizing antibodies. However, Env structure and organization in its native virion context has eluded detailed ...HIV-1 Env mediates viral entry into host cells and is the sole target for neutralizing antibodies. However, Env structure and organization in its native virion context has eluded detailed characterization. Here, we used cryo-electron tomography to analyze Env in mature and immature HIV-1 particles. Immature particles showed distinct Env positioning relative to the underlying Gag lattice, providing insights into long-standing questions about Env incorporation. A 9.1-Å sub-tomogram-averaged reconstruction of virion-bound Env in conjunction with structural mass spectrometry revealed unexpected features, including a variable central core of the gp41 subunit, heterogeneous glycosylation between protomers, and a flexible stalk that allows Env tilting and variable exposure of neutralizing epitopes. Together, our results provide an integrative understanding of HIV assembly and structural variation in Env antigen presentation.
External linksCell / PubMed:35123651 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution9.1 - 34.0 Å
Structure data

25178

7ska

EMDB-25178, PDB-7ska:
Sub-tomogram averaged structure of HIV-1 Envelope protein in native membrane
Method: EM (subtomogram averaging) / Resolution: 9.1 Å

EMDB-25186:
Asymmetric reconstruction of membrane-bound HIV Env from virus-like particles
Method: EM (subtomogram averaging) / Resolution: 10.67 Å

EMDB-25809:
Sub-tomogram averaged map of HIV-Env with Gag layer from immature VLPs
Method: EM (subtomogram averaging) / Resolution: 34.0 Å

Chemicals

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

ChemComp-FUC:
alpha-L-fucopyranose / Fucose

Source
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / HIV-1 / envelope protein / glycoprotein / Env / membrane bound

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