Complete virion assembly with scaffolding proteins altered in the ability to perform a critical conformational switch

James E. Cherwa, Bentley A Fane

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In the φX174 procapsid, 240 external scaffolding proteins form a nonquasiequivalent lattice. To achieve this arrangement, the four structurally unique subunits must undergo position-dependent conformational switches. One switch is mediated by glycine residue 61, which allows a 30° kink to form in α-helix 3 in two subunits, whereas the helix is straight in the other two subunits. No other amino acid should be able to produce a bend of this magnitude. Accordingly, all substitutions for G61 are nonviable but mutant proteins differ vis-à-vis recessive and dominant phenotypes. As previously reported, amino acid substitutions with side chains larger than valine confer dominant lethal phenotypes. Alone, these mutant proteins appear to have little or no biological activity but rather require the wild-type protein to interact with other structural proteins. Proteins with conservative substitutions for G61, serine and alanine, have now been characterized. Unlike the dominant lethal proteins, these proteins do not require wild-type subunits to interact with other viral proteins and cause assembly defects reminiscent of those conferred by the lethal dominant proteins in concert with wild-type subunits. Although atomic structures suggest that only a glycine residue can provide the proper torsion angle for assembly, mutants that can productively utilize the altered external scaffolding proteins were isolated, and the mutations were mapped to the coat and internal scaffolding proteins. Thus, the ability to isolate strains that could utilize the single mutant D protein species would not have been predicted from past structural analyses.

Original languageEnglish (US)
Pages (from-to)7391-7396
Number of pages6
JournalJournal of Virology
Volume83
Issue number15
DOIs
StatePublished - Aug 2009

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scaffolding proteins
virion
Virion
Proteins
proteins
lethal genes
Mutant Proteins
mutants
glycine (amino acid)
Glycine
phenotype
Phenotype
viral proteins
structural proteins
amino acid substitution
valine
Valine
Viral Proteins
Amino Acid Substitution
alanine

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Complete virion assembly with scaffolding proteins altered in the ability to perform a critical conformational switch. / Cherwa, James E.; Fane, Bentley A.

In: Journal of Virology, Vol. 83, No. 15, 08.2009, p. 7391-7396.

Research output: Contribution to journalArticle

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