Journal article
CryoET structures of immature HIV Gag reveal six-helix bundle
Communications biology, Vol.4(1), pp.481-481
04/16/2021
DOI: 10.1038/s42003-021-01999-1
PMCID: PMC8052356
PMID: 33863979
Abstract
Gag is the HIV structural precursor protein which is cleaved by viral protease to produce mature infectious viruses. Gag is a polyprotein composed of MA (matrix), CA (capsid), SP1, NC (nucleocapsid), SP2 and p6 domains. SP1, together with the last eight residues of CA, have been hypothesized to form a six-helix bundle responsible for the higher-order multimerization of Gag necessary for HIV particle assembly. However, the structure of the complete six-helix bundle has been elusive. Here, we determined the structures of both Gag in vitro assemblies and Gag viral-like particles (VLPs) to 4.2 Å and 4.5 Å resolutions using cryo-electron tomography and subtomogram averaging by emClarity. A single amino acid mutation (T8I) in SP1 stabilizes the six-helix bundle, allowing to discern the entire CA-SP1 helix connecting to the NC domain. These structures provide a blueprint for future development of small molecule inhibitors that can lock SP1 in a stable helical conformation, interfere with virus maturation, and thus block HIV-1 infection.
Mendonça et al. determine the structures of both in vitro assemblies of the HIV structural precursor protein Gag and Gag viral-like particles (VLPs) to 4.2 Å and 4.5 Å resolutions, using cryo-electron tomography and subtomogram averaging. This study provides insights into the future development of small molecule inhibitors for HIV-1 infection.
Details
- Title: Subtitle
- CryoET structures of immature HIV Gag reveal six-helix bundle
- Creators
- Luiza Mendonça - University of OxfordDapeng Sun - Centre for Human GeneticsJiying Ning - University of PittsburghJiwei Liu - University of OxfordAbhay Kotecha - Thermo Fisher Scientific (Netherlands)Mateusz Olek - Diamond Light SourceThomas Frosio - Diamond Light SourceXiaofeng Fu - University of PittsburghBenjamin A. Himes - University of PittsburghAlex B. Kleinpeter - Center for Cancer ResearchEric O. Freed - Center for Cancer ResearchJing Zhou - Vanderbilt University Medical CenterChristopher Aiken - Vanderbilt University Medical CenterPeijun Zhang - Diamond Light Source
- Resource Type
- Journal article
- Publication Details
- Communications biology, Vol.4(1), pp.481-481
- DOI
- 10.1038/s42003-021-01999-1
- PMID
- 33863979
- PMCID
- PMC8052356
- NLM abbreviation
- Commun Biol
- ISSN
- 2399-3642
- eISSN
- 2399-3642
- Publisher
- Nature Publishing Group UK
- Grant note
- BB/S003339/1 / RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (https://doi.org/10.13039/501100000268) 203141/Z/16/Z / Wellcome Trust (Wellcome) (https://doi.org/10.13039/100004440) AI150481 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) (https://doi.org/10.13039/100000002)
- Language
- English
- Date published
- 04/16/2021
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984826360202771
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