Please use this identifier to cite or link to this item:
Title: The Crystal Structure of Pneumolysin at 2.0 Å Resolution Reveals the Molecular Packing of the Pre-pore Complex
Authors: Marshall, Jamie E.
Faraj, Bayan H. A.
Gingras, Alexandre R.
Lonnen, Rana
Arif Sheikh, Md.
El-Mezgueldi, Mohammed
Moody, Peter C. E.
Andrew, Peter W.
Wallis, Russell
First Published: 3-Sep-2015
Publisher: Nature Publishing Group
Citation: Scientific Reports, 2015, 5 : 13293
Abstract: Pneumolysin is a cholesterol-dependent cytolysin (CDC) and virulence factor of Streptococcus pneumoniae. It kills cells by forming pores assembled from oligomeric rings in cholesterol-containing membranes. Cryo-EM has revealed the structures of the membrane-surface bound pre-pore and inserted-pore oligomers, however the molecular contacts that mediate these oligomers are unknown because high-resolution information is not available. Here we have determined the crystal structure of full-length pneumolysin at 1.98 Å resolution. In the structure, crystal contacts demonstrate the likely interactions that enable polymerisation on the cell membrane and the molecular packing of the pre-pore complex. The hemolytic activity is abrogated in mutants that disrupt these intermolecular contacts, highlighting their importance during pore formation. An additional crystal structure of the membrane-binding domain alone suggests that changes in the conformation of a tryptophan rich-loop at the base of the toxin promote monomer-monomer interactions upon membrane binding by creating new contacts. Notably, residues at the interface are conserved in other members of the CDC family, suggesting a common mechanism for pore and pre-pore assembly.
DOI Link: 10.1038/srep13293
eISSN: 2045-2322
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015, the authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

Files in This Item:
File Description SizeFormat 
srep13293.pdfPublished (publisher PDF)2.02 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.