Genetic studies of the β-hairpin loop of Rous sarcoma virus capsid protein

Jared L. Spidel, Carol B. Wilson, Rebecca C. Craven, John W. Wills

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


The first few residues of the Rous sarcoma virus (RSV) CA protein comprise a structurally dynamic region that forms part of a Gag-Gag interface in immature virus particles. Dissociation of this interaction during maturation allows refolding and formation of a β-hairpin structure important for assembly of CA monomers into the mature capsid shell. A consensus binding site for the cellular Ubc9 protein was previously identified within this region, suggesting that binding of Ubc9 and subsequent small ubiquitin-like modifier protein 1 (SUMO-1) modification of CA may play a role either in regulating the assembly activity of CA in immature particles or mature cores or in controlling postentry function (s) during the establishment of infection. In the present study, mutations designed to eliminate the consensus binding site were used to dissect the potentially overlapping functions of these residues. The resulting replication defects could not be traced to a failure to form particles of normal composition but, rather, to a deficit in genome replication. Genetic suppressors of two detrimental β-hairpin mutations improved infectivity without restoring the consensus site or creating a novel one elsewhere. Optimal restoration of infectivity to a Lys-to-Arg mutant required a combination of secondary changes, one on the surface of each domain of CA. Rather than arguing for a critical role of Ubc9 and SUMO in RSV replication, these findings provide strong support for a structural role of the N-terminal residues and a particularly striking example of long-range interactions between regions of CA in achieving a functional core competent for genome replication.

Original languageEnglish (US)
Pages (from-to)1288-1296
Number of pages9
JournalJournal of virology
Issue number3
StatePublished - Feb 2007

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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