---
_id: '816'
abstract:
- lang: eng
text: 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.
acknowledgement: The authors thank B. Glass for preparation of the immature HIV-1
(D25A) sample; J. Plitzko and D. Tegunov for providing the K2Align software; and
S. Mattei, N. Hoffman, F. Thommen, A. Sonnen, and S. Dodonova for technical assistance
and/or discussion. 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.). The Briggs laboratory acknowledges
financial support from the European Molecular Biology Laboratory (EMBL) and from
the Chica und Heinz Schaller Stiftung. W.W. was supported by a European Molecular
Biology Organization Long-Term Fellowship (ALTF 748-2014). A.J.J. acknowledges support
by the EMBL Interdisciplinary Postdoc Program under the Marie Curie Action COFUND
(PCOFUND-GA-2008-229597) and by the Joachim Herz Stiftung. This study was technically
supported by the EMBL information technology services unit and the EMBL Proteomics
Core Facility. F.K.M.S., M.O., H.-G.K., and J.A.G.B. designed the experiments, with
J.M.K. assisting in the design of those involving mass spectrometry. F.K.M.S. and
M.O. prepared samples. W.J.H.H. implemented tomography acquisition schemes. F.K.M.S.
and W.J.H.H. acquired the data. F.K.M.S. and W.W. processed images. F.K.M.S., A.J.J.,
and C.S. refined the model. F.K.M.S., M.O., and J.A.G.B. analyzed the data. F.K.M.S.
and J.A.G.B. wrote the manuscript with support from all authors. Representative
tomograms and the final electron microscopy structures have been deposited in the
Electron Microscopy Data Bank with accession numbers EMD-4015, EMD-4016, EMD-4017,
EMD-4018, EMD-4019, and EMD-4020. The refined HIV-1 CA-SP1 model has been deposited
in the Protein Data Bank with accession number 5L93.
article_processing_charge: No
author:
- first_name: Florian
full_name: Schur, Florian
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Martin
full_name: Obr, Martin
id: 4741CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Obr
orcid: 0000-0003-1756-6564
- first_name: Wim
full_name: Hagen, Wim
last_name: Hagen
- first_name: William
full_name: Wan, William
last_name: Wan
- first_name: Arjen
full_name: Jakobi, Arjen
last_name: Jakobi
- first_name: Joanna
full_name: Kirkpatrick, Joanna
last_name: Kirkpatrick
- first_name: Carsten
full_name: Sachse, Carsten
last_name: Sachse
- first_name: Hans
full_name: Kraüsslich, Hans
last_name: Kraüsslich
- first_name: John
full_name: Briggs, John
last_name: Briggs
citation:
ama: Schur FK, Obr M, Hagen W, et al. An Atomic Model of HIV-1 Capsid-SP1 Reveals
Structures Regulating Assembly and Maturation. Vol 353. American Association
for the Advancement of Science; 2016:506-508. doi:10.1126/science.aaf9620
apa: Schur, F. K., Obr, M., Hagen, W., Wan, W., Jakobi, A., Kirkpatrick, J., … Briggs,
J. (2016). An atomic model of HIV-1 capsid-SP1 reveals structures regulating
assembly and maturation (Vol. 353, pp. 506–508). American Association for
the Advancement of Science. https://doi.org/10.1126/science.aaf9620
chicago: Schur, Florian KM, Martin Obr, Wim Hagen, William Wan, Arjen Jakobi, Joanna
Kirkpatrick, Carsten Sachse, Hans Kraüsslich, and John Briggs. An Atomic Model
of HIV-1 Capsid-SP1 Reveals Structures Regulating Assembly and Maturation.
Vol. 353. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aaf9620.
ieee: F. K. Schur et al., An atomic model of HIV-1 capsid-SP1 reveals
structures regulating assembly and maturation, vol. 353. American Association
for the Advancement of Science, 2016, pp. 506–508.
ista: Schur FK, Obr M, Hagen W, Wan W, Jakobi A, Kirkpatrick J, Sachse C, Kraüsslich
H, Briggs J. 2016. An atomic model of HIV-1 capsid-SP1 reveals structures regulating
assembly and maturation, American Association for the Advancement of Science,p.
mla: Schur, Florian KM, et al. An Atomic Model of HIV-1 Capsid-SP1 Reveals Structures
Regulating Assembly and Maturation. Vol. 353, American Association for the
Advancement of Science, 2016, pp. 506–08, doi:10.1126/science.aaf9620.
short: F.K. Schur, M. Obr, W. Hagen, W. Wan, A. Jakobi, J. Kirkpatrick, C. Sachse,
H. Kraüsslich, J. Briggs, An Atomic Model of HIV-1 Capsid-SP1 Reveals Structures
Regulating Assembly and Maturation, American Association for the Advancement of
Science, 2016.
date_created: 2018-12-11T11:48:39Z
date_published: 2016-07-29T00:00:00Z
date_updated: 2026-05-20T07:41:16Z
day: '29'
doi: 10.1126/science.aaf9620
extern: '1'
external_id:
pmid:
- '27417497'
intvolume: ' 353'
language:
- iso: eng
month: '07'
oa_version: None
page: 506 - 508
pmid: 1
publication_identifier:
eissn:
- 1095-9203
issn:
- 0036-8075
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '6834'
scopus_import: '1'
status: public
title: An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly
and maturation
type: report
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 353
year: '2016'
...