RNA Synthesis in a Cage--Structural Studies of Reovirus Polymerase lambda3

Cell. 2002 Nov 27;111(5):733-45. doi: 10.1016/s0092-8674(02)01110-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Capsid / chemistry
  • Capsid / metabolism
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA, Double-Stranded / biosynthesis
  • RNA, Messenger / metabolism
  • RNA, Viral / biosynthesis*
  • Reoviridae / metabolism*
  • Structure-Activity Relationship
  • Substrate Specificity
  • Viral Core Proteins / chemistry
  • Viral Core Proteins / metabolism*

Substances

  • RNA, Double-Stranded
  • RNA, Messenger
  • RNA, Viral
  • Viral Core Proteins
  • DNA-Directed RNA Polymerases

Associated data

  • PDB/1MUK
  • PDB/1MWH
  • PDB/1N1H
  • PDB/1N35
  • PDB/1N38