Conformation of the HIV-1 Gag Protein in Solution
Open accessAbstract
A single multi-domain viral protein, termed Gag, is sufficient for assembly of retrovirus-like particles in mammalian cells. We have purified the human immunodeficiency virus type 1 (HIV-1) Gag protein (lacking myristate at its N terminus and the p6 domain at its C terminus) from bacteria. This protein is capable of assembly into virus-like particles in a defined in vitro system. We have reported that it is in monomer-dimer equilibrium in solution, and have described a mutant Gag protein that remains monomeric at high concentrations in solution. We report that the mutant protein retains several properties of wild-type Gag. This mutant enabled us to analyze solutions of monomeric protein. Hydrodynamic studies on the mutant protein showed that it is highly asymmetric, with a frictional ratio of 1.66. Small-angle neutron scattering (SANS) experiments confirmed its asymmetry and yielded an R(g) value of 34 A. Atomic-level structures of individual domains within Gag have previously been determined, but these domains are connected in Gag by flexible linkers. We constructed a series of models of the mutant Gag protein based on these domain structures, and tested each model computationally for its agreement with the experimental hydrodynamic and SANS data. The only models consistent with the data were those in which Gag was folded over, with its N-terminal matrix domain near its C-terminal nucleocapsid domain in three-dimensional space. Since Gag is a rod-shaped molecule in the assembled immature virion, these findings imply that Gag undergoes a major conformational change upon virus assembly.
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In the absence of nucleic acid, Gag shows weak protein-protein interactions and flexibly adopts different conformations; in HIV these include a compact arrangement in which MA folds back to interact with NC.
“In the absence of nucleic acid, Gag shows weak proteinprotein interactions and flexibly adopts different conformations; in HIV these include a compact arrangement in which MA folds back to interact with NC”
From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [17]
Cites
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Self-citationRetrovirus maturation-an extraordinary structural transformation
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“Assembly of immature retrovirus particles In the absence of nucleic acid, Gag shows weak proteinprotein interactions and flexibly adopts different conformations; in HIV these include a compact arrangement in which MA folds back to interact with NC [17].”
BackgroundBaratam, K., & Srivastava, A. (2024) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.4c00579 · Cited by 9 · see citing works
- Authors
- Datta, S. A. K., Curtis, J. E., Ratcliff, W., Clark, P. K., Crist, R. M., Lebowitz, J., Krueger, S., & Rein, A.
- Affiliations
- National Cancer Institute (US)
- National Institute of Standards and Technology (US)
- Science Applications International Corporation (United States) (US)
- National Institutes of Health (US)
- Corresponding author
- Rein, Alan
- ORCID
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 365
- Issue
- 3
- Pages
- 812-824
- ISSN
- 0022-2836 (ISSN-L)
- PMC
- PMC1866279
- OpenAlex
- W2138720208
- Cited by
- 145
- References
- 10
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 11 · 2017: 6 · 2016: 12 · 2015: 9 · 2014: 15 · 2013: 6 · 2012: 8
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01co12400-79-0-22, 1z01bc010511-05)
- National Cancer Institute (N01CO12400, N01-CO-012400, Z01 BC010511-03)
- NIST Center for Neutron Research
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- HIV-1 Gag protein, protein conformation, monomer-dimer equilibrium, virus-like particle assembly, hydrodynamic characteristics, small-angle neutron scattering, flexible linkers, protein folding, matrix domain, nucleocapsid domain
- MeSH terms
- Circular Dichroism, Humans, Models, Molecular, Mutation, Protein Conformation, Solutions, HIV-1, Gene Products, gag, Neutron Diffraction, Mutant Proteins, Scattering, Small Angle
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