The Receptor Binding Domain of Botulinum Neurotoxin Stereotype C Binds Phosphoinositides

Journal Article · Thu Mar 01 04:00:00 EST 2012 · Biochimie (Paris)

DOI:https://doi.org/10.1016/j.biochi.2011.11.004· OSTI ID:1037956

Zhang, Yanfeng; Varnum, Susan M

Botulinum neurotoxins (BoNTs) are the most toxic proteins known for humans and animals with an extremely low LD50 of {approx} 1 ng/kg. BoNTs generally require a protein and a ganglioside on the cell membrane surface for binding, which is known as a 'dual receptor' mechanism for host intoxication. Recent studies have suggested that in addition to gangliosides, other membrane lipids such as phosphoinositides may be involved in the interactions with the receptor binding domain (HCR) of BoNTs for better membrane penetration. Here, using two independent lipid-binding assays, we tested the interactions of BoNT/C-HCR with lipids in vitro. BoNT/C-HCR was found to bind negatively charged phospholipids, preferentially phosphoinositides. Additional interactions to phosphoinositides may help BoNT/C bind membrane more tightly and transduct signals for subsequent steps of intoxication. Our results provide new insights into the mechanisms of host cell membrane recognition by BoNTs.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1037956
• Report Number(s): PNNL-SA-82952; 400412000
• Journal Information: Biochimie (Paris), Journal Name: Biochimie (Paris) Journal Issue: 3 Vol. 94; ISSN 0300-9084; ISSN BICMBE
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ANIMALS
BoNT/C
Botulinumneurotoxin
Botulism
CELL MEMBRANES
GANGLIOSIDES
IN VITRO
LIPIDS
MEMBRANES
Membrane binding
PHOSPHOLIPIDS
PROTEINS
Phosphoinositides