Journal article
Conformational Changes during Pore Formation by the Perforin-Related Protein Pleurotolysin
N Lukoyanova, SC Kondos, I Farabella, RHP Law, CF Reboul, TT Caradoc-Davies, BA Spicer, O Kleifeld, DAK Traore, SM Ekkel, I Voskoboinik, JA Trapani, T Hatfaludi, K Oliver, EM Hotze, RK Tweten, JC Whisstock, M Topf, HR Saibil, MA Dunstone
Plos Biology | Published : 2015
Abstract
Membrane attack complex/perforin-like (MACPF) proteins comprise the largest superfamily of pore-forming proteins, playing crucial roles in immunity and pathogenesis. Soluble monomers assemble into large transmembrane pores via conformational transitions that remain to be structurally and mechanistically characterised. Here we present an 11 Å resolution cryo-electron microscopy (cryo-EM) structure of the two-part, fungal toxin Pleurotolysin (Ply), together with crystal structures of both components (the lipid binding PlyA protein and the pore-forming MACPF component PlyB). These data reveal a 13-fold pore 80 Å in diameter and 100 Å in height, with each subunit comprised of a PlyB molecule ato..
View full abstractGrants
Awarded by European Commission
Funding Acknowledgements
HRS acknowledges support from the Wellcome Trust (grant 079605/2/06/2) for EM facilities and doctoral training support to KO (MRC G1001602), the BBSRC (BB/D00873/1) and the ERC (294408). MT acknowledges the BBSRC (BB/K01692X/1) and Leverhulme Trust (RPG-2012-519). We thank D. Houldershaw and R. Westlake for computing support, L. Wang for EM support, and E.V. Orlova, D.K. Clare and A.P. Pandurangan for discussion. MAD is a National Health and Medical Research Council of Australia (NHMRC) Career Development Fellow. MAD acknowledges support from the Australian Research Council (ARC) [DP120104058, DP0986811, CE140100011] and the National Health and Medical Research Council [606471]. JCW is an NHMRC Senior Principal Research Fellow. JCW also acknowledges the support of an Australian Research Council Federation Fellowship. CFR is supported by the Australian Postgraduate Award. DT acknowledges the support of an ARC Super Science Fellowship. RKT acknowledges the National Institutes of Health, NIAID [AI037657]. The authors acknowledge the support of the Victorian Life Sciences Computation Initiative (VLSCI, Melbourne, Australia) and the Multi-modal Australian ScienceS Imaging and Visualisation Environment (MASSIVE) (www.massive.org.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.