Structural basis of the ribosomal machinery for peptide bond formation, translocation, and nascent chain progression

Mol Cell. 2003 Jan;11(1):91-102. doi: 10.1016/s1097-2765(03)00009-1.

Abstract

Crystal structures of tRNA mimics complexed with the large ribosomal subunit of Deinococcus radiodurans indicate that remote interactions determine the precise orientation of tRNA in the peptidyl-transferase center (PTC). The PTC tolerates various orientations of puromycin derivatives and its flexibility allows the conformational rearrangements required for peptide-bond formation. Sparsomycin binds to A2602 and alters the PTC conformation. H69, the intersubunit-bridge connecting the PTC and decoding site, may also participate in tRNA placement and translocation. A spiral rotation of the 3' end of the A-site tRNA around a 2-fold axis of symmetry identified within the PTC suggests a unified ribosomal machinery for peptide-bond formation, A-to-P-site translocation, and entrance of nascent proteins into the exit tunnel. Similar 2-fold related regions, detected in all known structures of large ribosomal subunits, indicate the universality of this mechanism.

Publication types

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

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Catalytic Domain
  • Crystallography, X-Ray
  • Deinococcus / genetics*
  • Models, Molecular
  • Molecular Structure
  • Nucleic Acid Conformation*
  • Protein Biosynthesis*
  • Protein Conformation*
  • Protein Synthesis Inhibitors / chemistry
  • Protein Synthesis Inhibitors / metabolism
  • Puromycin / chemistry
  • Puromycin / metabolism
  • RNA, Transfer, Amino Acyl / chemistry*
  • RNA, Transfer, Amino Acyl / genetics
  • RNA, Transfer, Amino Acyl / metabolism
  • Ribosomal Proteins / chemistry*
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Sparsomycin / chemistry
  • Sparsomycin / metabolism

Substances

  • Bacterial Proteins
  • Protein Synthesis Inhibitors
  • RNA, Transfer, Amino Acyl
  • Ribosomal Proteins
  • Puromycin
  • Sparsomycin

Associated data

  • PDB/1NJM
  • PDB/1NJN
  • PDB/1NJO
  • PDB/1NJP