Structure of the N-terminal 283-residue fragment of the immature HIV-1 Gag polyprotein
Abstract
The capsid protein (CA) of the mature human immunodeficiency virus (HIV) contains an N-terminal beta-hairpin that is essential for formation of the capsid core particle. CA is generated by proteolytic cleavage of the Gag precursor polyprotein during viral maturation. We have determined the NMR structure of a 283-residue N-terminal fragment of immature HIV-1 Gag (Gag(283)), which includes the intact matrix (MA) and N-terminal capsid (CA(N)) domains. The beta-hairpin is unfolded in Gag(283), consistent with the proposal that hairpin formation occurs subsequent to proteolytic cleavage of Gag, triggering capsid assembly. Comparison of the immature and mature CA(N) structures reveals that beta-hairpin formation induces a approximately 2 A displacement of helix 6 and a concomitant displacement of the cyclophylin-A (CypA)-binding loop, suggesting a possible allosteric mechanism for CypA-mediated destabilization of the capsid particle during infectivity.
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A beta-hairpin is formed by the N-terminal residues in mature-like CA, stabilized by a salt bridge between the N-terminal proline and a conserved aspartate in helix 3.
“A beta-hairpin is formed by the N-terminal residues in mature-like CA, stabilized by a salt bridge between the N-terminal proline and a conserved aspartate in helix 3”
From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [10]
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- Authors
- Tang, C., Ndassa, Y., & Summers, M. F.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Summers, Michael F.
- Venue
- Nature Structural Biology
- Published
- 2002-05-28
- Volume
- 9
- Issue
- 7
- Pages
- 537-43
- ISSN
- 1072-8368 (ISSN-L)
- OpenAlex
- W2055673257
- Cited by
- 205
- References
- 55
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 9 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 13 · 2015: 11 · 2014: 10 · 2013: 17 · 2012: 12
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1 Gag polyprotein, capsid protein, capsid assembly, matrix domain, proteolytic cleavage, cyclophilin A, virus maturation, NMR structure
- MeSH terms
- Amino Acid Sequence, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Protein Precursors, Viral Proteins, HIV Antigens, HIV-1, Gene Products, gag, Protein Structure, Secondary, Protein Structure, Tertiary, Virus Assembly, Nucleocapsid Proteins, Nuclear Magnetic Resonance, Biomolecular, Cyclophilin A, gag Gene Products, Human Immunodeficiency Virus, Hydrophobic and Hydrophilic Interactions
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