Co-translational Folding Intermediate Dictates Membrane Targeting of the Signal Recognition Particle Receptor

J Mol Biol. 2018 May 25;430(11):1607-1620. doi: 10.1016/j.jmb.2018.04.017. Epub 2018 Apr 25.


Much of our knowledge on the function of proteins is deduced from their mature, folded states. However, it is unknown whether partially synthesized nascent protein segments can execute biological functions during translation and whether their premature folding states matter. A recent observation that a nascent chain performs a distinct function, co-translational targeting in vivo, has been made with the Escherichia coli signal recognition particle receptor FtsY, a major player in the conserved pathway of membrane protein biogenesis. FtsY functions as a membrane-associated entity, but very little is known about the mode of its targeting to the membrane. Here we investigated the underlying structural mechanism of the co-translational FtsY targeting to the membrane. Our results show that helices N2-4, which mediate membrane targeting, form a stable folding intermediate co-translationally that greatly differs from its fold in the mature FtsY. These results thus resolve a long-standing mystery of how the receptor targets the membrane even when deleted of its alleged membrane targeting sequence. The structurally distinct targeting determinant of FtsY exists only co-translationally. Our studies will facilitate further efforts to seek cellular factors required for proper targeting and association of FtsY with the membrane. Moreover, the results offer a hallmark example for how co-translational nascent intermediates may dictate biological functions.

Keywords: FtsY structures; SRP receptor FtsY; co-translational folding; co-translational targeting; ribosome targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Escherichia coli / metabolism*
  • Models, Molecular
  • Protein Binding
  • Protein Biosynthesis*
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Transport
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Ribosomes / metabolism


  • Bacterial Proteins
  • FtsY protein, Bacteria
  • Receptors, Cytoplasmic and Nuclear