Cited by 49HIV Research and TreatmentMass Spectrometry Techniques and ApplicationsHIV/AIDS drug development and treatment

Hydrogen/Deuterium Exchange Analysis of HIV-1 Capsid Assembly and Maturation

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Monroe, Eric B., Kang, Sebyung, Kyere, Sampson K., Li, Rui, Prevelige, Peter E.·2010·Structure

Abstract

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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Crossref · 10.1016/j.str.2010.08.016

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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.”

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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)
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
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

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