Leung, C; Dudkina, NV; Lukoyanova, N; Hodel, AW; Farabella, I; Pandurangan, AP; Jahan, N; ... Hoogenboom, BW; + view all Leung, C; Dudkina, NV; Lukoyanova, N; Hodel, AW; Farabella, I; Pandurangan, AP; Jahan, N; Pires Damaso, M; Osmanović, D; Reboul, CF; Dunstone, MA; Andrew, PW; Lonnen, R; Topf, M; Saibil, HR; Hoogenboom, BW; - view fewer (2014) Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin. Elife , 3 , Article e04247. 10.7554/eLife.04247.

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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.

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