Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin

Carl Leung, Natalya V Dudkina, Natalya Lukoyanova, Adrian W. Hodel, Irene Farabella, Arun P. Pandurangan, Nasrin Jahan, Mafalda Pires Damaso, Dino Osmanović, Cyril F Reboul, Michelle A Dunstone, Peter W. Andrew, Rana Lonnen, Maya Topf, Helen Ruth Saibil, Bart W. Hoogenboom

Research output: Contribution to journalArticleResearchpeer-review

108 Citations (Scopus)

Abstract

Membrane attack complex/perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins constitute a major superfamily of pore-forming proteins that act as bacterial virulence factors and effectors in immune defence. Upon binding to the membrane, they convert from the soluble monomeric form to oligomeric, membrane-inserted pores. Using real-time atomic force microscopy (AFM), electron microscopy (EM), and atomic structure fitting, we have mapped the structure and assembly pathways of a bacterial CDC in unprecedented detail and accuracy, focussing on suilysin from Streptococcus suis. We show that suilysin assembly is a noncooperative process that is terminated before the protein inserts into the membrane. The resulting ring-shaped pores and kinetically trapped arc-shaped assemblies are all seen to perforate the membrane, as also visible by the ejection of its lipids. Membrane insertion requires a concerted conformational change of the monomeric subunits, with a marked expansion in pore diameter due to large changes in subunit structure and packing.

Original languageEnglish
Article numbere04247
Number of pages17
JournaleLife
Volume3
DOIs
Publication statusPublished - 2014

Keywords

  • bacterial toxins
  • biophysics
  • cholesterol-dependent cytolysins
  • membrane pore formation
  • pore-forming proteins
  • S. suis
  • structural biology

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