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Potential role for CA-SP in nucleating retroviral capsid maturation.
- Source :
-
Journal of virology [J Virol] 2014 Jul; Vol. 88 (13), pp. 7170-7. Date of Electronic Publication: 2014 Apr 09. - Publication Year :
- 2014
-
Abstract
- Unlabelled: During virion maturation, the Rous sarcoma virus (RSV) capsid protein is cleaved from the Gag protein as the proteolytic intermediate CA-SP. Further trimming at two C-terminal sites removes the spacer peptide (SP), producing the mature capsid proteins CA and CA-S. Abundant genetic and structural evidence shows that the SP plays a critical role in stabilizing hexameric Gag interactions that form immature particles. Freeing of CA-SP from Gag breaks immature interfaces and initiates the formation of mature capsids. The transient persistence of CA-SP in maturing virions and the identification of second-site mutations in SP that restore infectivity to maturation-defective mutant viruses led us to hypothesize that SP may play an important role in promoting the assembly of mature capsids. This study presents a biophysical and biochemical characterization of CA-SP and its assembly behavior. Our results confirm cryo-electron microscopy (cryo-EM) structures reported previously by Keller et al. (J. Virol. 87:13655-13664, 2013, doi:10.1128/JVI.01408-13) showing that monomeric CA-SP is fully capable of assembling into capsid-like structures identical to those formed by CA. Furthermore, SP confers aggressive assembly kinetics, which is suggestive of higher-affinity CA-SP interactions than observed with either of the mature capsid proteins. This aggressive assembly is largely independent of the SP amino acid sequence, but the formation of well-ordered particles is sensitive to the presence of the N-terminal β-hairpin. Additionally, CA-SP can nucleate the assembly of CA and CA-S. These results suggest a model in which CA-SP, once separated from the Gag lattice, can actively promote the interactions that form mature capsids and provide a nucleation point for mature capsid assembly.<br />Importance: The spacer peptide is a documented target for antiretroviral therapy. This study examines the biochemical and biophysical properties of CA-SP, an intermediate form of the retrovirus capsid protein. The results demonstrate a previously unrecognized activity of SP in promoting capsid assembly during maturation.<br /> (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Amino Acid Sequence
Capsid Proteins genetics
Capsid Proteins metabolism
Cryoelectron Microscopy
Humans
Models, Molecular
Molecular Sequence Data
Peptide Fragments genetics
Peptide Fragments metabolism
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Capsid metabolism
Capsid Proteins chemistry
Peptide Fragments chemistry
Rous sarcoma virus physiology
Virus Assembly
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 88
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 24719425
- Full Text :
- https://doi.org/10.1128/JVI.00309-14