Three-dimensional structure of the anthrax toxin pore inserted into lipid nanodiscs and lipid vesicles.
Proc Natl Acad Sci U S A
; 107(8): 3453-7, 2010 Feb 23.
Article
in En
| MEDLINE
| ID: mdl-20142512
ABSTRACT
A major goal in understanding the pathogenesis of the anthrax bacillus is to determine how the protective antigen (PA) pore mediates translocation of the enzymatic components of anthrax toxin across membranes. To obtain structural insights into this mechanism, we constructed PA-pore membrane complexes and visualized them by using negative-stain electron microscopy. Two populations of PA pores were visualized in membranes, vesicle-inserted and nanodisc-inserted, allowing us to reconstruct two virtually identical PA-pore structures at 22-A resolution. Reconstruction of a domain 4-truncated PA pore inserted into nanodiscs showed that this domain does not significantly influence pore structure. Normal mode flexible fitting of the x-ray crystallographic coordinates of the PA prepore indicated that a prominent flange observed within the pore lumen is formed by the convergence of mobile loops carrying Phe427, a residue known to catalyze protein translocation. Our results have identified the location of a crucial functional element of the PA pore and documented the value of combining nanodisc technology with electron microscopy to examine the structures of membrane-interactive proteins.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bacterial Toxins
/
Cell Membrane
/
Nanoparticles
/
Antigens, Bacterial
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2010
Document type:
Article
Affiliation country:
United States