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TitleAn atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation.
Journal, issue, pagesScience, Vol. 353, Issue 6298, Page 506-508, Year 2016
Publish dateJul 29, 2016
AuthorsFlorian K M Schur / Martin Obr / Wim J H Hagen / William Wan / Arjen J Jakobi / Joanna M Kirkpatrick / Carsten Sachse / Hans-Georg Kräusslich / John A G Briggs /
PubMed AbstractImmature HIV-1 assembles at and buds from the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation can be blocked by maturation ...Immature HIV-1 assembles at and buds from the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation can be blocked by maturation inhibitors (MIs), thereby abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation and is the target of MIs. We applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 angstrom resolution and built an atomic model. The structure reveals a network of intra- and intermolecular interactions mediating immature HIV-1 assembly. The proteolytic cleavage site between CA and SP1 is inaccessible to protease. We suggest that MIs prevent CA-SP1 cleavage by stabilizing the structure, and MI resistance develops by destabilizing CA-SP1.
External linksScience / PubMed:27417497
MethodsEM (subtomogram averaging) / EM (tomography)
Resolution3.9 - 4.5 Å
Structure data

4015

5l93

EMDB-4015: A 3.9 Angstrom structure of HIV-1 CA-SP1 assembled in presence of Bevirimat
PDB-5l93: An atomic model of HIV-1 CA-SP1 reveals structures regulating assembly and maturation
Method: EM (subtomogram averaging) / Resolution: 3.9 Å

EMDB-4016:
A 4.5 Angstrom structure of HIV-1 CA-SP1
Method: EM (subtomogram averaging) / Resolution: 4.5 Å

EMDB-4017:
A 4.2 Angstrom structure of HIV-1 CA-SP1 from immature HIV-1 particles
Method: EM (subtomogram averaging) / Resolution: 4.2 Å

EMDB-4018:
Cryo-electron tomogram containing HIV-1 deltaMACANC virus-like particles assembled in vitro in presence of Bevirimat
Method: EM (tomography)

EMDB-4019:
Cryo-electron tomogram containing HIV-1 deltaMACANC virus-like particles assembled in vitro
Method: EM (tomography)

EMDB-4020:
Cryo-electron tomogram containing immature HIV-1 particles
Method: EM (tomography)

Source
  • human immunodeficiency virus type 1 group m subtype b (isolate ny5)
KeywordsVIRAL PROTEIN / HIV-1 capsid SP1

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