A role for the two-helix finger of the SecA ATPase in protein translocation

Nature. 2008 Oct 16;455(7215):984-7. doi: 10.1038/nature07439.


An important step in the biosynthesis of many proteins is their partial or complete translocation across the plasma membrane in prokaryotes or the endoplasmic reticulum membrane in eukaryotes. In bacteria, secretory proteins are generally translocated after completion of their synthesis by the interaction of the cytoplasmic ATPase SecA and a protein-conducting channel formed by the SecY complex. How SecA moves substrates through the SecY channel is unclear. However, a recent structure of a SecA-SecY complex raises the possibility that the polypeptide chain is moved by a two-helix finger domain of SecA that is inserted into the cytoplasmic opening of the SecY channel. Here we have used disulphide-bridge crosslinking to show that the loop at the tip of the two-helix finger of Escherichia coli SecA interacts with a polypeptide chain right at the entrance into the SecY pore. Mutagenesis demonstrates that a tyrosine in the loop is particularly important for translocation, but can be replaced by some other bulky, hydrophobic residues. We propose that the two-helix finger of SecA moves a polypeptide chain into the SecY channel with the tyrosine providing the major contact with the substrate, a mechanism analogous to that suggested for hexameric, protein-translocating ATPases.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Amino Acid Motifs
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cross-Linking Reagents
  • Disulfides / chemistry
  • Disulfides / metabolism
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Models, Biological
  • Models, Molecular
  • Protein Conformation
  • Protein Transport
  • SEC Translocation Channels
  • SecA Proteins
  • Structure-Activity Relationship
  • Tyrosine / metabolism


  • Bacterial Proteins
  • Cross-Linking Reagents
  • Disulfides
  • Escherichia coli Proteins
  • Membrane Transport Proteins
  • SEC Translocation Channels
  • SecY protein, E coli
  • Tyrosine
  • Adenosine Triphosphatases
  • SecA Proteins