Marshall, Jamie E, Faraj, Bayan H A, Gingras, Alexandre R, Lonnen, Rana, Sheikh, Md. Arif, El-Mezgueldi, Mohammed, Moody, Peter C E, Andrew, Peter W and Wallis, Russell (2015) The crystal structure of Pneumolysin at 2.0 Å resolution reveals the molecular packing of the pre-pore complex. Scientific Reports, 5. pp. 1-11. ISSN 2045-2322
![]() |
PDF
- Published Version
Available under License Creative Commons Attribution. Download (2MB) |
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.
Item Type: | Article |
---|---|
Schools and Departments: | School of Life Sciences > Sussex Centre for Genome Damage and Stability |
Subjects: | Q Science > QR Microbiology > QR0001 General |
Depositing User: | MD Arif Sheikh |
Date Deposited: | 18 Sep 2015 13:09 |
Last Modified: | 18 Mar 2022 11:30 |
URI: | http://sro.sussex.ac.uk/id/eprint/56826 |
View download statistics for this item
📧 Request an update