Structural basis for the interaction of protein S1 with the Escherichia coli ribosome

Nucleic Acids Res. 2015 Jan;43(1):661-73. doi: 10.1093/nar/gku1314. Epub 2014 Dec 15.


In Gram-negative bacteria, the multi-domain protein S1 is essential for translation initiation, as it recruits the mRNA and facilitates its localization in the decoding centre. In sharp contrast to its functional importance, S1 is still lacking from the high-resolution structures available for Escherichia coli and Thermus thermophilus ribosomes and thus the molecular mechanism governing the S1-ribosome interaction has still remained elusive. Here, we present the structure of the N-terminal S1 domain D1 when bound to the ribosome at atomic resolution by using a combination of NMR, X-ray crystallography and cryo-electron microscopy. Together with biochemical assays, the structure reveals that S1 is anchored to the ribosome primarily via a stabilizing π-stacking interaction within the short but conserved N-terminal segment that is flexibly connected to domain D1. This interaction is further stabilized by salt bridges involving the zinc binding pocket of protein S2. Overall, this work provides one hitherto enigmatic piece in the 'ribosome puzzle', namely the detailed molecular insight into the topology of the S1-ribosome interface. Moreover, our data suggest novel mechanisms that have the potential to modulate protein synthesis in response to environmental cues by changing the affinity of S1 for the ribosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / genetics
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • Ribosomal Proteins / chemistry*
  • Ribosomal Proteins / metabolism
  • Ribosome Subunits, Small, Bacterial / metabolism
  • Ribosomes / chemistry*
  • Ribosomes / metabolism


  • Escherichia coli Proteins
  • Ribosomal Proteins
  • ribosomal protein S1, E coli
  • ribosomal protein S2