Mirror-Image 5S Ribonucleoprotein Complexes

Angew Chem Int Ed Engl. 2020 Feb 24;59(9):3724-3731. doi: 10.1002/anie.201914799. Epub 2020 Jan 21.

Abstract

After realizing mirror-image genetic replication, transcription, and reverse transcription, the biggest challenge in establishing a mirror-image version of the central dogma is to build a mirror-image ribosome-based translation machine. Here, we chemically synthesized the natural and mirror-image versions of three ribosomal proteins (L5, L18, and L25) in the large subunit of the Escherichia coli ribosome with post-translational modifications. We show that the synthetic mirror-image proteins can fold in vitro despite limited efficiency and assemble with enzymatically transcribed mirror-image 5S ribosomal RNA into ribonucleoprotein complexes. In addition, the RNA-protein interactions are chiral-specific in that the mirror-image ribosomal proteins do not bind with natural 5S ribosomal RNA and vice versa. The synthesis and assembly of mirror-image 5S ribonucleoprotein complexes are important steps towards building a functional mirror-image ribosome.

Keywords: chemical protein synthesis; chirality; native chemical ligation; ribonucleoproteins; solid-phase peptide synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / metabolism
  • Protein Binding
  • RNA, Ribosomal, 5S / chemistry
  • RNA, Ribosomal, 5S / metabolism*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Ribosomal Proteins / chemical synthesis
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Ribosomes / metabolism
  • Stereoisomerism

Substances

  • Escherichia coli Proteins
  • RNA, Ribosomal, 5S
  • Recombinant Proteins
  • Ribosomal Proteins
  • ribosomal protein L18
  • ribosomal protein L25