Hydrogen/Deuterium Exchange Analysis of HIV-1 Capsid Assembly and Maturation
Open accessAbstract
Following budding, HIV-1 virions undergo a maturation process where the Gag polyprotein in the immature virus is cleaved by the viral protease and rearranges to form the mature infectious virion. Despite the wealth of structures of isolated capsid domains and an in vitro-assembled mature lattice, models of the immature lattice do not provide an unambiguous model of capsid-molecule orientation and no structural information is available for the capsid maturation pathway. Here we have applied hydrogen/deuterium exchange mass spectrometry to immature, mature, and mutant Gag particles (CA5) blocked at the final Gag cleavage event to examine the molecular basis of capsid assembly and maturation. Capsid packing arrangements were very similar for all virions, whereas immature and CA5 virions contained an additional intermolecular interaction at the hexameric, 3-fold axis. Additionally, the N-terminal β-hairpin was observed to form as a result of capsid-SP1 cleavage rather than driving maturation as previously postulated.
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Hydrogen/deuterium exchange rates supported increased protection in the beta-hairpin and NTD-CTD interface in mature virions, which had not formed in the Gag/CA5 structural intermediate.
“H/D exchange rates supported increased protection in the β-hairpin and the NTD-CTD interface in mature virions, which interestingly had yet to form in the Gag/CA5 structural intermediate.”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [31]
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- Authors
- Monroe, E. B., Kang, S., Kyere, S. K., Li, R., & Prevelige, P. E.
- Affiliations
- University of Alabama at Birmingham (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Prevelige, Peter E.
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 18
- Issue
- 11
- Pages
- 1483-1491
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC2982214
- OpenAlex
- W2053607817
- Cited by
- 49
- References
- 37
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2017: 4 · 2016: 2 · 2015: 6 · 2014: 9 · 2013: 7 · 2012: 5
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1025 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- National Institutes of Health (F31GM076979, F32GM087994, R01AI044626, R37AI30917)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1 capsid, capsid assembly, capsid maturation, Gag protein, immature virions
- MeSH terms
- Capsid, Electrophoresis, Polyacrylamide Gel, Models, Molecular, Mass Spectrometry, Virion, HIV-1, Deuterium Exchange Measurement
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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