Invited Speaker The 48th Lorne Conference on Protein Structure and Function 2023

Protein folding within the bacterial outer membrane (#41)

Matthew Doyle 1
  1. School of Medical Sciences, The University of Sydney, Camperdown, NSW, Australia

The Gram-negative bacterial outer membrane (OM) is densely packed with β-barrel outer membrane proteins (OMPs) which vary greatly in size (8-36 strands). Despite their structural and functional diversity, almost all newly synthesised OMPs are folded and integrated into the OM by the essential Barrel Assembly Machine (BAM). However, the molecular process of OMP folding by BAM has remained largely a mystery. Major questions include: (1) how are new OMPs recognized by BAM? (2) what are the intermediate stages of OMP folding? (3) what is the energy source for folding? To solve these questions, we tracked protein folding in bacterial culture and observed folding intermediates in native-nanodiscs by CryoEM. Our data leads to unique models explaining how OMPs are folded via “barrelization” and a new idea in which the OM macrostructure can power OMP folding at the molecular level.