5CR8

Structure of the membrane-binding domain of pneumolysin

Summary for 5CR8

• Entry DOI: 10.2210/pdb5cr8/pdb
• Descriptor: Pneumolysin (2 entities in total)
• Functional Keywords: toxin, cholesterol-dependent cytolysin, virulence factor, hydrolase
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 26425.58

Authors

Marshall, J.E.,Faraj, B.H.A.,Gingras, A.R.,Lonnen, R.,Sheikh, M.A.,El-Mezgueldi, M.,Moody, P.C.E.,Andrew, P.W.,Wallis, R. (deposition date: 2015-07-22, release date: 2015-09-16, Last modification date: 2024-01-10)

Primary citation

Marshall, J.E.,Faraj, B.H.,Gingras, A.R.,Lonnen, R.,Sheikh, M.A.,El-Mezgueldi, M.,Moody, P.C.,Andrew, P.W.,Wallis, R.
The Crystal Structure of Pneumolysin at 2.0 angstrom Resolution Reveals the Molecular Packing of the Pre-pore Complex.
Sci Rep, 5:13293-13293, 2015

PubMed 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.

PubMed: 26333773
DOI: 10.1038/srep13293

Experimental method

X-RAY DIFFRACTION (2.05 Å)