Imperial College London

Emeritus ProfessorJohnSeddon

Faculty of Natural SciencesDepartment of Chemistry

Senior Research Investigator
 
 
 
//

Contact

 

+44 (0)20 7594 5797j.seddon Website

 
 
//

Location

 

207EMolecular Sciences Research HubWhite City Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Boyd:2016:10.1038/srep38446,
author = {Boyd, C and Parsons, ES and Smith, RAG and Seddon, JM and Ces, O and Bubeck, D},
doi = {10.1038/srep38446},
journal = {Scientific Reports},
title = {Disentangling the roles of cholesterol and CD59 in intermedilysin pore formation},
url = {http://dx.doi.org/10.1038/srep38446},
volume = {6},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The plasma membrane provides an essential barrier, shielding a cell from the pressures of its external environment. Pore-forming proteins, deployed by both hosts and pathogens alike, breach this barrier to lyse target cells. Intermedilysin is a cholesterol-dependent cytolysin that requires the human immune receptor CD59, in addition to cholesterol, to form giant β-barrel pores in host membranes. Here we integrate biochemical assays with electron microscopy and atomic force microscopy to distinguish the roles of these two receptors in mediating structural transitions of pore formation. CD59 is required for the specific coordination of intermedilysin (ILY) monomers and for triggering collapse of an oligomeric prepore. Movement of Domain 2 with respect to Domain 3 of ILY is essential for forming a late prepore intermediate that releases CD59, while the role of cholesterol may be limited to insertion of the transmembrane segments. Together these data define a structural timeline for ILY pore formation and suggest a mechanism that is relevant to understanding other pore-forming toxins that also require CD59.
AU - Boyd,C
AU - Parsons,ES
AU - Smith,RAG
AU - Seddon,JM
AU - Ces,O
AU - Bubeck,D
DO - 10.1038/srep38446
PY - 2016///
SN - 2045-2322
TI - Disentangling the roles of cholesterol and CD59 in intermedilysin pore formation
T2 - Scientific Reports
UR - http://dx.doi.org/10.1038/srep38446
UR - http://hdl.handle.net/10044/1/42380
VL - 6
ER -