Characterization of a Streptococcal Cholesterol-Dependent Cytolysin with a Lewis y and b Specific Lectin Domain

2008/06/14 by Stephen Farrand, Eileen M. Hotze, Paul Friese +5 · 65 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Immunology and Microbiology · Medicine · #Bacteria #Biochemistry #Biology #Cell wall #Chemistry #Cytolysin #Fucose #Gene #Glycan #Glycoprotein #Lectin #Lipid Membrane Structure and Behavior #Pneumolysin #Streptococcal Infections and Treatments #Streptococcus #Streptococcus mitis #Streptococcus pneumoniae #Toxin Mechanisms and Immunotoxins #Xyloglucan

paper · open access · doi:10.1021/bi8005835

published in Biochemistry 47(27), 7097-7107 (American Chemical Society)

openalex publication_date 2008/06/14 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

The cholesterol-dependent cytolysins (CDCs) are a large family of pore-forming toxins that often exhibit distinct structural changes that modify their pore-forming activity. A soluble platelet aggregation factor from Streptococcus mitis (Sm-hPAF) was characterized and shown to be a functional CDC with an amino-terminal fucose-binding lectin domain. Sm-hPAF, or lectinolysin (LLY) as renamed herein, is most closely related to CDCs from Streptococcus intermedius (ILY) and Streptococcus pneumoniae (pneumolysin or PLY). The LLY gene was identified in strains of S. mitis, S. pneumoniae, and Streptococcus pseudopneumoniae. LLY induces pore-dependent changes in the light scattering properties of the platelets that mimic those induced by platelet aggregation but does not induce platelet aggregation. LLY monomers form the typical large homooligomeric membrane pore complex observed for the CDCs. The pore-forming activity of LLY on platelets is modulated by the amino-terminal lectin domain, a structure that is not present in other CDCs. Glycan microarray analysis showed the lectin domain is specific for difucosylated glycans within Lewis b (Le (b)) and Lewis y (Le (y)) antigens. The glycan-binding site is occluded in the soluble monomer of LLY but is apparently exposed after cell binding, since it significantly increases LLY pore-forming activity in a glycan-dependent manner. Hence, LLY represents a new class of CDC whose pore-forming mechanism is modulated by a glycan-binding domain.

Citations

• Identification of a Membrane-Spanning Domain of the Thiol-Activated Pore-Forming Toxin Clostridium perfringens Perfringolysin O: An α-Helical to β-Sheet Transition Identified by Fluorescence Spectroscopy
• Redefining cholesterol's role in the mechanism of the cholesterol-dependent cytolysins
• Vertical collapse of a cytolysin prepore moves its transmembrane β‐hairpins to the membrane
• Arresting Pore Formation of a Cholesterol-dependent Cytolysin by Disulfide Trapping Synchronizes the Insertion of the Transmembrane β-Sheet from a Prepore Intermediate
• Structural insights into the membrane-anchoring mechanism of a cholesterol-dependent cytolysin
• The Mechanism of Pore Assembly for a Cholesterol-Dependent Cytolysin: Formation of a Large Prepore Complex Precedes the Insertion of the Transmembrane β-Hairpins

Cited by

• The Cholesterol-Dependent Cytolysin Family of Gram-Positive Bacterial Toxins
• Cholesterol-dependent cytolysin [wikipedia]

Related

• The Cholesterol-Dependent Cytolysin Signature Motif: A Critical Element in the Allosteric Pathway that Couples Membrane Binding to Pore Assembly
• Only two amino acids are essential for cytolytic toxin recognition of cholesterol at the membrane surface
• Structural elements of the cholesterol-dependent cytolysins that are responsible for their cholesterol-sensitive membrane interactions
• Conformational Changes That Effect Oligomerization and Initiate Pore Formation Are Triggered throughout Perfringolysin O upon Binding to Cholesterol
• Monomer-Monomer Interactions Propagate Structural Transitions Necessary for Pore Formation by the Cholesterol-dependent Cytolysins