Molecular basis for the folding of β-helical autotransporter passenger domains

Research output: Contribution to journalArticlepeer-review

Authors

  • Xiaojun Yuan
  • Matthew D Johnson
  • Jing Zhang
  • Alvin W Lo
  • Mark A Schembri
  • Lakshmi C Wijeyewickrema
  • Robert N Pike
  • Gerard H M Huysmans
  • Denisse L Leyton

Colleges, School and Institutes

External organisations

  • Research School of Biology, Australian National University, Canberra, ACT, 0200, Australia.
  • Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, QLD, 4072, Australia.
  • Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
  • Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10065, USA.
  • Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK. n.j.loman@bham.ac.uk.
  • Medical School, Australian National University, Canberra, ACT, 0200, Australia. denisse.leyton@anu.edu.au.

Abstract

Bacterial autotransporters comprise a C-terminal β-barrel domain, which must be correctly folded and inserted into the outer membrane to facilitate translocation of the N-terminal passenger domain to the cell exterior. Once at the surface, the passenger domains of most autotransporters are folded into an elongated β-helix. In a cellular context, key molecules catalyze the assembly of the autotransporter β-barrel domain. However, how the passenger domain folds into its functional form is poorly understood. Here we use mutational analysis on the autotransporter Pet to show that the β-hairpin structure of the fifth extracellular loop of the β-barrel domain has a crucial role for passenger domain folding into a β-helix. Bioinformatics and structural analyses, and mutagenesis of a homologous autotransporter, suggest that this function is conserved among autotransporter proteins with β-helical passenger domains. We propose that the autotransporter β-barrel domain is a folding vector that nucleates folding of the passenger domain.

Details

Original languageEnglish
Article number1395
JournalNature Communications
Volume9
Issue number1
Publication statusPublished - 11 Apr 2018