Quaternary dynamics of the SecA motor drive translocase catalysis

Mol Cell. 2013 Dec 12;52(5):655-66. doi: 10.1016/j.molcel.2013.10.036.

Abstract

Most secretory preproteins exit bacterial cells through the protein translocase, comprising the SecYEG channel and the dimeric peripheral ATPase motor SecA. Energetic coupling to work remains elusive. We now demonstrate that translocation is driven by unusually dynamic quaternary changes in SecA. The dimer occupies several successive states with distinct protomer arrangements. SecA docks on SecYEG as a dimer and becomes functionally asymmetric. Docking occurs via only one protomer. The second protomer allosterically regulates downstream steps. Binding of one preprotein signal peptide to the SecYEG-docked SecA protomer elongates the SecA dimer and triggers the translocase holoenzyme to obtain a lower activation energy conformation. ATP hydrolysis monomerizes the triggered SecA dimer, causing mature chain trapping and processive translocation. This is a unique example of one protein exploiting quaternary dynamics to become a substrate receptor, a "loading clamp," and a "processive motor." This mechanism has widespread implications on protein translocases, chaperones, and motors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Catalysis
  • Dimerization
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Hydrolysis
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism*
  • Mutation
  • Protein Binding
  • Protein Conformation
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport
  • SEC Translocation Channels
  • SecA Proteins

Substances

  • Bacterial Proteins
  • Membrane Transport Proteins
  • Protein Subunits
  • SEC Translocation Channels
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • SecA Proteins