A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion

Citations Over TimeTop 10% of 2016 papers

Abstract

The conserved SecYEG protein-conducting channel and the accessory proteins SecDF-YajC and YidC constitute the bacterial holo-translocon (HTL), capable of protein-secretion and membrane-protein insertion. By employing an integrative approach combining small-angle neutron scattering (SANS), low-resolution electron microscopy and biophysical analyses we determined the arrangement of the proteins and lipids within the super-complex. The results guided the placement of X-ray structures of individual HTL components and allowed the proposal of a model of the functional translocon. Their arrangement around a central lipid-containing pool conveys an unexpected, but compelling mechanism for membrane-protein insertion. The periplasmic domains of YidC and SecD are poised at the protein-channel exit-site of SecY, presumably to aid the emergence of translocating polypeptides. The SecY lateral gate for membrane-insertion is adjacent to the membrane 'insertase' YidC. Absolute-scale SANS employing a novel contrast-match-point analysis revealed a dynamic complex adopting open and compact configurations around an adaptable central lipid-filled chamber, wherein polytopic membrane-proteins could fold, sheltered from aggregation and proteolysis.

Related Papers

• → Protein translocation across the inner membrane of Gram-negative bacteria: the Sec and Tat dependent protein transport pathways(2013)179 cited
• → Intracellular trafficking of MAN1, an integral protein of the nuclear envelope inner membrane(2002)90 cited
• → Membrane Insertion and Topology of the Translocating Chain-Associating Membrane Protein (TRAM)(2011)37 cited
• Determinants of membrane protein topology(1999)
• Insertion and Topology of Inner Membrane Proteins in Escherichia coli(1999)