Crystal structure of an RNA bacteriophage coat protein–operator complex

Abstract

THE RNA bacteriophage MS2 is a convenient model system for the study of protein–RNA interactions. The MS2 coat protein achieves control of two distinct processes—sequence-specific RNA encapsidation and repression of replicase translation—by binding to an RNA stem–loop structure of 19 nucleotides containing the initiation codon of the replicase gene. The binding of a coat protein dimer to this hairpin shuts off synthesis of the viral replicase¹, switching the viral replication cycle to virion assembly rather than continued replication. The operator fragment alone can trigger self-assembly of the phage capsid at low protein concentrations and a complex of about 90 RNA operator fragments per protein capsid has been described². We report here the crystal structure at 3.0 Å resolution of a complex between recombinant MS2 cap-sids and the 19-nucleotide RNA fragment. It is the first example of a structure at this resolution for a sequence-specific protein-RNA complex apart from the transfer RNA synthetase complexes^3–5. The structure shows sequence-specific interactions between conserved residues on the protein and RNA bases essential for binding.