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TitleHigh-resolution structures of HIV-1 Gag cleavage mutants determine structural switch for virus maturation.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 115, Issue 40, Page E9401-E9410, Year 2018
Publish dateOct 2, 2018
AuthorsSimone Mattei / Aaron Tan / Bärbel Glass / Barbara Müller / Hans-Georg Kräusslich / John A G Briggs /
PubMed AbstractHIV-1 maturation occurs via multiple proteolytic cleavages of the Gag polyprotein, causing rearrangement of the virus particle required for infectivity. Cleavage results in beta-hairpin formation at ...HIV-1 maturation occurs via multiple proteolytic cleavages of the Gag polyprotein, causing rearrangement of the virus particle required for infectivity. Cleavage results in beta-hairpin formation at the N terminus of the CA (capsid) protein and loss of a six-helix bundle formed by the C terminus of CA and the neighboring SP1 peptide. How individual cleavages contribute to changes in protein structure and interactions, and how the mature, conical capsid forms, are poorly understood. Here, we employed cryoelectron tomography to determine morphology and high-resolution CA lattice structures for HIV-1 derivatives in which Gag cleavage sites are mutated. These analyses prompt us to revise current models for the crucial maturation switch. Unlike previously proposed, cleavage on either terminus of CA was sufficient, in principle, for lattice maturation, while complete processing was needed for conical capsid formation. We conclude that destabilization of the six-helix bundle, rather than beta-hairpin formation, represents the main determinant of structural maturation.
External linksProc Natl Acad Sci U S A / PubMed:30217893 / PubMed Central
MethodsEM (subtomogram averaging) / EM (tomography)
Resolution3.7 - 24.0 Å
Structure data

EMDB-0164:
Immature CA domain from HIV-1 MA-SP1 Gag proteolytic cleavage mutant virus particles
Method: EM (subtomogram averaging) / Resolution: 4.0 Å

EMDB-0165:
Immature CA domain from HIV-1 MA-CA Gag proteolytic cleavage mutant virus particles
Method: EM (subtomogram averaging) / Resolution: 3.7 Å

EMDB-0166:
Immature CA domain from HIV-1 CA-NC Gag proteolytic cleavage mutant virus particles
Method: EM (subtomogram averaging) / Resolution: 4.5 Å

EMDB-0167:
Mature CA domain hexamer from HIV-1 MA-CA Gag proteolytic cleavage mutant virus particles
Method: EM (subtomogram averaging) / Resolution: 8.3 Å

EMDB-0168:
Mature CA domain hexamer from HIV-1 CA-NC Gag proteolytic cleavage mutant virus particles
Method: EM (subtomogram averaging) / Resolution: 9.7 Å

EMDB-0169:
Mature CA domain hexamer from HIV-1 CA-SP1 Gag proteolytic cleavage mutant virus particles
Method: EM (subtomogram averaging) / Resolution: 7.9 Å

EMDB-0170:
Mature CA domain pentamer from HIV-1 CA-NC Gag proteolytic cleavage mutant virus particles
Method: EM (subtomogram averaging) / Resolution: 22.0 Å

EMDB-0171:
Mature CA domain pentamer from HIV-1 CA-SP1 Gag proteolytic cleavage mutant virus particles
Method: EM (subtomogram averaging) / Resolution: 24.0 Å

EMDB-13079:
Representative cryo-electron tomogram of HIV-1 MA-SP1 particles
Method: EM (tomography)

EMDB-13080:
Representative cryo-electron tomogram of HIV-1 MA-CA particles
Method: EM (tomography)

Source
  • Homo sapiens (human)

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