DOI: 10.7554/elife.17063. Crystal structure of an HIV assembly and maturation switch

Crystal structure of an HIV assembly and maturation switch

10.7554/elife.17063

Crossref journal-article

eLife Sciences Publications, Ltd

eLife (4374)

Abstract

Virus assembly and maturation proceed through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an ensuing type II β-turn, and the stem comprises a 6-helix bundle. The β-turn is critical for immature virus assembly and the 6-helix bundle regulates proteolysis during maturation. This bipartite character explains why the SP1 spacer is a critical element of HIV-1 Gag but is not a universal property of retroviruses. Our results also indicate that HIV-1 maturation inhibitors suppress unfolding of the CA-SP1 junction and thereby delay access of the viral protease to its substrate.

Authors 7

Jonathan M Wagner (first)
Kaneil K Zadrozny (additional)
Jakub Chrustowicz (additional)
Michael D Purdy (additional)
Mark Yeager (additional)
Barbie K Ganser-Pornillos (additional)
Owen Pornillos (additional)

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Dates

Type	When
Created	9 years, 1 month ago (July 14, 2016, 9:16 a.m.)
Deposited	1 year, 10 months ago (Oct. 11, 2023, 8:53 p.m.)
Indexed	3 weeks, 2 days ago (Aug. 3, 2025, 7:03 p.m.)
Issued	9 years, 1 month ago (July 14, 2016)
Published	9 years, 1 month ago (July 14, 2016)
Published Online	9 years, 1 month ago (July 14, 2016)

Funders 4

National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01-GM066087
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. P50-GM082545
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. P50-GM103297
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. F32-GM115007

BibTeX

@article{Wagner_2016, title={Crystal structure of an HIV assembly and maturation switch}, volume={5}, ISSN={2050-084X}, url={http://dx.doi.org/10.7554/elife.17063}, DOI={10.7554/elife.17063}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Wagner, Jonathan M and Zadrozny, Kaneil K and Chrustowicz, Jakub and Purdy, Michael D and Yeager, Mark and Ganser-Pornillos, Barbie K and Pornillos, Owen}, year={2016}, month=jul }

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  "abstract": "<jats:p>Virus assembly and maturation proceed through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an ensuing type II \u03b2-turn, and the stem comprises a 6-helix bundle. The \u03b2-turn is critical for immature virus assembly and the 6-helix bundle regulates proteolysis during maturation. This bipartite character explains why the SP1 spacer is a critical element of HIV-1 Gag but is not a universal property of retroviruses. Our results also indicate that HIV-1 maturation inhibitors suppress unfolding of the CA-SP1 junction and thereby delay access of the viral protease to its substrate.</jats:p>",
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