---
_id: '809'
abstract:
- lang: eng
text: The assembly of HIV-1 is mediated by oligomerization of the major structural
polyprotein, Gag, into a hexameric protein lattice at the plasma membrane of the
infected cell. This leads to budding and release of progeny immature virus particles.
Subsequent proteolytic cleavage of Gag triggers rearrangement of the particles
to form mature infectious virions. Obtaining a structural model of the assembled
lattice of Gag within immature virus particles is necessary to understand the
interactions that mediate assembly of HIV-1 particles in the infected cell, and
to describe the substrate that is subsequently cleaved by the viral protease.
An 8-Å resolution structure of an immature virus-like tubular array assembled
from a Gag-derived protein of the related retrovirus Mason-Pfizer monkey virus
(M-PMV) has previously been reported, and a model for the arrangement of the HIV-1
capsid (CA) domains has been generated based on homology to this structure. Here
we have assembled tubular arrays of a HIV-1 Gag-derived protein with an immature-like
arrangement of the C-terminal CA domains and have solved their structure by using
hybrid cryo-EM and tomography analysis. The structure reveals the arrangement
of the C-terminal domain of CA within an immature-like HIV-1 Gag lattice, and
provides, to our knowledge, the first high-resolution view of the region immediately
downstream of CA, which is essential for assembly, and is significantly different
from the respective region in M-PMV. Our results reveal a hollow column of density
for this region in HIV-1 that is compatible with the presence of a six-helix bundle
at this position.
acknowledgement: 'The authors thank Leonardo Trabuco for help with running MDFF, Maria
Anders for preparing amprenavir-inhibited virus, Marie-Christine Vaney for help
with X-ray data processing and structure refinement, Ahmed Haouz and Patrick Weber
(robotized crystallization facility Proteopole, Institut Pasteur) for help in crystal
screening, and the European Molecular Biology Laboratory (EMBL) Information Technology
Services Unit and Frank Thommen for technical support. This study was supported
by Deutsche Forschungsgemeinschaft Grants BR 3635/2-1 (to J.A.G.B.) and KR 906/7-1
(to H.-G.K.) and a Federation of European Biochemical Societies long-term fellowship
(to T.A.M.B.). The laboratory of J.A.G.B. acknowledges financial support from EMBL
and the Chica und Heinz Schaller Stiftung. '
author:
- first_name: Tanmay
full_name: Bharata, Tanmay A
last_name: Bharata
- first_name: Luis
full_name: Menendez, Luis R
last_name: Menendez
- first_name: Wim
full_name: Hagena, Wim J
last_name: Hagena
- first_name: Vanda
full_name: Luxd, Vanda
last_name: Luxd
- first_name: Sebastien
full_name: Igonete, Sebastien
last_name: Igonete
- first_name: Martin
full_name: Schorba, Martin
last_name: Schorba
- first_name: Florian
full_name: Florian Schur
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Hans
full_name: Kraüsslich, Hans Georg
last_name: Kraüsslich
- first_name: John
full_name: Briggsa, John A
last_name: Briggsa
citation:
ama: Bharata T, Menendez L, Hagena W, et al. Cryo electron microscopy of tubular
arrays of HIV-1 Gag resolves structures essential for immature virus assembly.
PNAS. 2014;111(22):8233-8238. doi:10.1073/pnas.1401455111
apa: Bharata, T., Menendez, L., Hagena, W., Luxd, V., Igonete, S., Schorba, M.,
… Briggsa, J. (2014). Cryo electron microscopy of tubular arrays of HIV-1 Gag
resolves structures essential for immature virus assembly. PNAS. National
Academy of Sciences. https://doi.org/10.1073/pnas.1401455111
chicago: Bharata, Tanmay, Luis Menendez, Wim Hagena, Vanda Luxd, Sebastien Igonete,
Martin Schorba, Florian KM Schur, Hans Kraüsslich, and John Briggsa. “Cryo Electron
Microscopy of Tubular Arrays of HIV-1 Gag Resolves Structures Essential for Immature
Virus Assembly.” PNAS. National Academy of Sciences, 2014. https://doi.org/10.1073/pnas.1401455111.
ieee: T. Bharata et al., “Cryo electron microscopy of tubular arrays of HIV-1
Gag resolves structures essential for immature virus assembly,” PNAS, vol.
111, no. 22. National Academy of Sciences, pp. 8233–8238, 2014.
ista: Bharata T, Menendez L, Hagena W, Luxd V, Igonete S, Schorba M, Schur FK, Kraüsslich
H, Briggsa J. 2014. Cryo electron microscopy of tubular arrays of HIV-1 Gag resolves
structures essential for immature virus assembly. PNAS. 111(22), 8233–8238.
mla: Bharata, Tanmay, et al. “Cryo Electron Microscopy of Tubular Arrays of HIV-1
Gag Resolves Structures Essential for Immature Virus Assembly.” PNAS, vol.
111, no. 22, National Academy of Sciences, 2014, pp. 8233–38, doi:10.1073/pnas.1401455111.
short: T. Bharata, L. Menendez, W. Hagena, V. Luxd, S. Igonete, M. Schorba, F.K.
Schur, H. Kraüsslich, J. Briggsa, PNAS 111 (2014) 8233–8238.
date_created: 2018-12-11T11:48:37Z
date_published: 2014-06-03T00:00:00Z
date_updated: 2021-01-12T08:16:50Z
day: '03'
doi: 10.1073/pnas.1401455111
extern: 1
intvolume: ' 111'
issue: '22'
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '06'
page: 8233 - 8238
publication: PNAS
publication_status: published
publisher: National Academy of Sciences
publist_id: '6838'
quality_controlled: 0
status: public
title: Cryo electron microscopy of tubular arrays of HIV-1 Gag resolves structures
essential for immature virus assembly
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
volume: 111
year: '2014'
...