A unifying mechanism for the biogenesis of membrane proteins co-operatively integrated by the Sec and Tat pathways

Elife. 2017 May 17:6:e26577. doi: 10.7554/eLife.26577.

Abstract

The majority of multi-spanning membrane proteins are co-translationally inserted into the bilayer by the Sec pathway. An important subset of membrane proteins have globular, cofactor-containing extracytoplasmic domains requiring the dual action of the co-translational Sec and post-translational Tat pathways for integration. Here, we identify further unexplored families of membrane proteins that are dual Sec-Tat-targeted. We establish that a predicted heme-molybdenum cofactor-containing protein, and a complex polyferredoxin, each require the concerted action of two translocases for their assembly. We determine that the mechanism of handover from Sec to Tat pathway requires the relatively low hydrophobicity of the Tat-dependent transmembrane domain. This, coupled with the presence of C-terminal positive charges, results in abortive insertion of this transmembrane domain by the Sec pathway and its subsequent release at the cytoplasmic side of the membrane. Together, our data points to a simple unifying mechanism governing the assembly of dual targeted membrane proteins.

Keywords: E. coli; Sec pathway; Tat pathway; biochemistry; infectious disease; membrane protein; microbiology; none; photosynthesis; protein translocation; respiration.

MeSH terms

  • Computational Biology
  • DNA Mutational Analysis
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Mutant Proteins / biosynthesis
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • SEC Translocation Channels / metabolism*
  • Streptomyces coelicolor / genetics
  • Twin-Arginine-Translocation System / metabolism*

Substances

  • Membrane Proteins
  • Mutant Proteins
  • Recombinant Proteins
  • SEC Translocation Channels
  • Twin-Arginine-Translocation System