Structure and function of the C-terminal domain of the polymerase cofactor of rabies virus.
The phosphoprotein (P) of rabies virus binds the viral polymerase to the nucleoprotein (N)-RNA template for transcription and replication. By limited protease digestion we defined a monomeric C-terminal domain of P that can bind to N-RNA. The atomic structure of this domain was determined and previously described mutations that interfere with binding of P to N-RNA could now be interpreted. There appears to be two features involved in this activity situated at opposite surfaces of the molecule: a positively charged patch and a hydrophobic pocket with an exposed tryptophan side-chain. Other previously published work suggests a conformational change in P when it binds to N-RNA, which may imply the repositioning of two helices that would expose a hydrophobic groove for interaction with N. This domain of rabies virus P is structurally unrelated to the N-RNA binding domains of the phosphoproteins of Sendai and measles virus that are members of the same order of viruses, the non-segmented negative strand RNA viruses. The implications of this finding for the evolution of this virus group are discussed.
EMBL Grenoble Outstation, BP181, 38042 Grenoble Cedex 9, France.
Manos
M
Mavrakis
Andrew A
AA
McCarthy
Stéphane
S
Roche
Danielle
D
Blondel
Rob W H
RW
Ruigrok
D000595:Amino Acid Sequence; D003067:Coenzymes / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D011820:Rabies virus / Q000737:chemistry* / Q000378:metabolism
D003067:Coenzymes; D010750:Phosphoproteins; D012324:RNA-Dependent RNA Polymerase