Potential role for CA-SP in nucleating retroviral capsid maturation

Matthew R. England, John G. Purdy, Ira Ropson, Paula Dalessio, Rebecca C. Cravena

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7170-7177
Number of pages8
JournalJournal of virology
Volume88
Issue number13
DOIs
StatePublished - Jan 1 2014

Fingerprint

capsid
Capsid
peptides
Peptides
Capsid Proteins
coat proteins
virion
Virion
immatures
Rous sarcoma virus
Defective Viruses
Cryoelectron Microscopy
gag Gene Products
Amino Acid Sequence

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

England, Matthew R. ; Purdy, John G. ; Ropson, Ira ; Dalessio, Paula ; Cravena, Rebecca C. / Potential role for CA-SP in nucleating retroviral capsid maturation. In: Journal of virology. 2014 ; Vol. 88, No. 13. pp. 7170-7177.
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Potential role for CA-SP in nucleating retroviral capsid maturation. / England, Matthew R.; Purdy, John G.; Ropson, Ira; Dalessio, Paula; Cravena, Rebecca C.

In: Journal of virology, Vol. 88, No. 13, 01.01.2014, p. 7170-7177.

Research output: Contribution to journalArticle

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