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TitleIn vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway.
Journal, issue, pagesNat Commun, Vol. 7, Page 13689, Year 2016
Publish dateDec 13, 2016
AuthorsJiying Ning / Gonca Erdemci-Tandogan / Ernest L Yufenyuy / Jef Wagner / Benjamin A Himes / Gongpu Zhao / Christopher Aiken / Roya Zandi / Peijun Zhang /
PubMed AbstractHIV-1 virions assemble as immature particles containing Gag polyproteins that are processed by the viral protease into individual components, resulting in the formation of mature infectious particles. ...HIV-1 virions assemble as immature particles containing Gag polyproteins that are processed by the viral protease into individual components, resulting in the formation of mature infectious particles. There are two competing models for the process of forming the mature HIV-1 core: the disassembly and de novo reassembly model and the non-diffusional displacive model. To study the maturation pathway, we simulate HIV-1 maturation in vitro by digesting immature particles and assembled virus-like particles with recombinant HIV-1 protease and monitor the process with biochemical assays and cryoEM structural analysis in parallel. Processing of Gag in vitro is accurate and efficient and results in both soluble capsid protein and conical or tubular capsid assemblies, seemingly converted from immature Gag particles. Computer simulations further reveal probable assembly pathways of HIV-1 capsid formation. Combining the experimental data and computer simulations, our results suggest a sequential combination of both displacive and disassembly/reassembly processes for HIV-1 maturation.
External linksNat Commun / PubMed:27958264 / PubMed Central
MethodsEM (subtomogram averaging) / EM (helical sym.)
Resolution18.0 - 22.0 Å
Structure data

EMDB-8403:
sub-tomogram average of in vitro assembled HIV-1 Gag VLPs
Method: EM (subtomogram averaging) / Resolution: 18.0 Å

EMDB-8404:
Single particle helical reconstruction of protease cleavage product from HIV-1 Gag VLPs
Method: EM (helical sym.) / Resolution: 22.0 Å

Source
  • Human immunodeficiency virus 1

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