Structural highlights
Publication Abstract from PubMed
Although pore formation by protective antigen (PA) is critical to cell intoxication by anthrax toxin (AT), the structure of the pore form of PA (the PA63 pore) has not been determined. Hence, in this study, the PA63 pore was modeled using the X-ray structures of monomeric PA and heptameric alpha-hemolysin (alpha-HL) as templates. The PA63 pore model consists of two weakly associated domains, namely the cap and stem domains. The ring-like cap domain has a length of 80 A and an outside diameter of 120 A, while the cylinder-like stem domain has a length of 100 A and outside diameter of approximately 28 A. This provides the PA63 pore model with a length of 180 A. Based on experimental results, the channel in the PA63 pore model was built to have a minimum diameter of ~12 A, depending on side chain conformations. Because of its large size and structural complexity, the all-atom model of the PA63 pore is the end-stage construction of four separate modeling projects described herein. The final model is consistent with published experimental results, including mutational analysis and channel conductance experiments. In addition, the model was energetically and hydropathically refined to optimize molecular packing within the protomers and at the protomer-protomer interfaces. By providing atomic detail to biochemical and biophysical data, the PA63 pore model may afford new insights into the binding mode of PA on the membrane surface, the prepore-pore transition, and the mechanism of cell entry by anthrax toxin.
Three-dimensional model of the pore form of anthrax protective antigen. Structure and biological implications.,Nguyen TL J Biomol Struct Dyn. 2004 Dec;22(3):253-65. PMID:15473701[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nguyen TL. Three-dimensional model of the pore form of anthrax protective antigen. Structure and biological implications. J Biomol Struct Dyn. 2004 Dec;22(3):253-65. PMID:15473701
