Cited by 206HIV Research and TreatmentMass Spectrometry Techniques and ApplicationsAdvanced Proteomics Techniques and Applications

Identification of Novel Interactions in HIV-1 Capsid Protein Assembly by High-resolution Mass Spectrometry

Lanman, Jason, Lam, TuKiet T., Barnes, Stephen, Sakalian, Michael, Emmett, Mark R., Marshall, Alan G., Prevelige, Peter E.·2003·Journal of Molecular Biology

Abstract

The pleomorphic nature of the immature and mature HIV-1 virions has made it difficult to characterize intersubunit interactions using traditional approaches. While the structures of isolated domains are known, the challenge is to identify intersubunit interactions and thereby pack these domains into supramolecular structures. Using high-resolution mass spectrometry, we have measured the amide hydrogen exchange protection factors for the soluble capsid protein (CA) and CA assembled in vitro. Comparison of the protection factors as well as chemical crosslinking experiments has led to a map of the subunit/subunit interfaces in the assembled tubes. This analysis provides direct biochemical evidence for the homotypic N domain and C domain interactions proposed from cryo-electron microscopy image reconstruction of CA tubes. Most significantly, we have identified a previously unrecognized intersubunit N domain-C domain interaction. The detection of this interaction reconciles previously discrepant biophysical and genetic data.

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Crossref · 10.1016/s0022-2836(02)01245-7

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  • An interface is also present between each CA-CTD and the CA-NTD of the neighbouring CA molecule in the hexameric ring.

    “An interface is also present between each CA-CTD and the CA-NTD of the neighbouring CA molecule in the hexameric ring”

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Authors
Lanman, J., Lam, T. T., Barnes, S., Sakalian, M., Emmett, M. R., Marshall, A. G., & Prevelige, P. E.
Affiliations
  • University of Alabama at Birmingham (US)
  • Florida State University (US)
  • University of Oklahoma Health Sciences Center (US)
Corresponding author
Prevelige, Peter E.
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2003-01
Volume
325
Issue
4
Pages
759-772
ISSN
0022-2836 (ISSN-L)
OpenAlex
W1968718594
Cited by
206
References
56
Citations by year
2026: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 7 · 2013: 14 · 2012: 8
FWCI
5.06
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • National High Magnetic Field Laboratory
  • National Institutes of Health (5r01gm031683-17)
  • National Cancer Institute (T32 CA 09467, T32CA009467)
  • National Institute of General Medical Sciences (GM 31683)
  • National Institute of Allergy and Infectious Diseases (AI 44626, R01AI044626)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
HIV-1 capsid protein, intersubunit interactions, amide hydrogen exchange, N-domain, C-domain, subunit interface, chemical crosslinking, supramolecular structure
MeSH terms
Amides, Cross-Linking Reagents, Deuterium, Hydrogen, Models, Molecular, Mass Spectrometry, HIV-1, Mutagenesis, Site-Directed, Protein Structure, Tertiary, Dimerization, Protein Structure, Quaternary, Protein Subunits, Capsid Proteins, Macromolecular Substances

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