RNA synthesis in a cage--structural studies of reovirus polymerase lambda3.
The reovirus polymerase and those of other dsRNA viruses function within the confines of a protein capsid to transcribe the tightly packed dsRNA genome segments. The crystal structure of the reovirus polymerase, lambda3, determined at 2.5 A resolution, shows a fingers-palm-thumb core, similar to those of other viral polymerases, surrounded by major N- and C-terminal elaborations, which create a cage-like structure, with four channels leading to the catalytic site. This "caged" polymerase has allowed us to visualize the results of several rounds of RNA polymerization directly in the crystals. A 5' cap binding site on the surface of lambda3 suggests a template retention mechanism by which attachment of the 5' end of the plus-sense strand facilitates insertion of the 3' end of the minus-sense strand into the template channel.
Tao
Yizhi
Y
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Farsetta
Diane L
DL
Nibert
Max L
ML
Harrison
Stephen C
SC
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis*; D012087:Reoviridae / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014758:Viral Core Proteins / Q000737:chemistry / Q000378:metabolism*
D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; D014758:Viral Core Proteins; D012321:DNA-Directed RNA Polymerases