Tom Edwards (Larkin U):

Structural Analysis of the Replication Complex in Respiratory Syncytial Virus

Human respiratory syncytial virus (HRSV) is an important human pathogen; it is the leading cause of lower respiratory tract illness in young children and the immunocompromised. HRSV is a non-segmented negative-strand RNA viruses. The M2-1 protein prevents premature transcription termination of the RNA-dependant RNA polymerase. The X-ray crystal structure reveals that M2-1 forms a tetramer driven by a long helix forming a four-helix bundle at its center and contacts between the zinc-binding domain and adjacent protomers. Structure-guided mutagenesis identified residues that contributed to RNA binding and antitermination activity.

The replication complex comprises the phosphoprotein (P) and the polymerase, whereas for transcription, M2-1 is also required. M2-1 is recruited to the RdRp by interaction with P and also interacts with RNA at overlapping binding sites on the M2-1 surface, such that binding of these partners is mutually exclusive. The crystal structure of M2-1 bound to the P interaction domain is also described.