Assembly mechanism of the oligomeric streptolysin O pore: the early membrane lesion is lined by a free edge of the lipid membrane and is extended gradually during oligomerization

Streptolysin O (SLO) is a bacterial exotoxin that binds to cell membranes containing cholesterol and then oligomerizes to form large pores. Along with rings, arc‐shaped oligomers form on membranes. It has been suggested that each arc represents an incompletely assembled oligomer and constitutes a fu...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 1998-03, Vol.17 (6), p.1598-1605
Main Authors: Palmer, Michael, Harris, Robin, Freytag, Claudia, Kehoe, Michael, Tranum-Jensen, Jørgen, Bhakdi, Sucharit
Format: Article
Language:English
Subjects:
Animals
Bacterial Proteins
Cell Membrane Permeability
Complement Hemolytic Activity Assay
Cysteine - chemistry
Erythrocyte Membrane - chemistry
Erythrocyte Membrane - metabolism
Erythrocyte Membrane - ultrastructure
Membrane Lipids - chemistry
Mutation
Naphthalenesulfonates
pore-forming toxins
Protein Conformation
protein oligomerization
Rabbits
streptolysin O
Streptolysins - chemistry
Streptolysins - genetics
thiol-activated toxins
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Streptolysin O (SLO) is a bacterial exotoxin that binds to cell membranes containing cholesterol and then oligomerizes to form large pores. Along with rings, arc‐shaped oligomers form on membranes. It has been suggested that each arc represents an incompletely assembled oligomer and constitutes a functional pore, faced on the opposite side by a free edge of the lipid membrane. We sought functional evidence in support of this idea by using an oligomerization‐deficient, non‐lytic mutant of SLO. This protein, which was created by chemical modification of a single mutant cysteine (T250C) with N‐(iodoacetaminoethyl)‐1‐naphthylamine‐5‐sulfonic acid, formed hybrid oligomers with active SLO on membranes. However, incorporation of the modified T250C mutant inhibited subsequent oligomerization, so that the hybrid oligomers were reduced in size. These appeared as typical arc lesions in the electron microscope. They formed pores that permitted passage of NaCl and calcein but restricted permeation of large dextran molecules. The data indicate that the SLO pore is formed gradually during oligomerization, implying that pores lined by protein on one side and an edge of free lipid on the other may be created in the plasma membrane. Intentional manipulation of the pore size may extend the utility of SLO as a tool in cell biological experiments.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/17.6.1598