Anthrax toxin translocation complex reveals insight into the lethal factor unfolding and refolding mechanism.
Sci Rep
; 11(1): 13038, 2021 06 22.
Article
en En
| MEDLINE
| ID: mdl-34158520
Translocation is essential to the anthrax toxin mechanism. Protective antigen (PA), the binding component of this AB toxin, forms an oligomeric pore that translocates lethal factor (LF) or edema factor, the active components of the toxin, into the cell. Structural details of the translocation process have remained elusive despite their biological importance. To overcome the technical challenges of studying translocation intermediates, we developed a method to immobilize, transition, and stabilize anthrax toxin to mimic important physiological steps in the intoxication process. Here, we report a cryoEM snapshot of PApore translocating the N-terminal domain of LF (LFN). The resulting 3.3 Å structure of the complex shows density of partially unfolded LFN near the canonical PApore binding site. Interestingly, we also observe density consistent with an α helix emerging from the 100 Å ß barrel channel suggesting LF secondary structural elements begin to refold in the pore channel. We conclude the anthrax toxin ß barrel aids in efficient folding of its enzymatic payload prior to channel exit. Our hypothesized refolding mechanism has broader implications for pore length of other protein translocating toxins.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Toxinas Bacterianas
/
Replegamiento Proteico
/
Desplegamiento Proteico
/
Antígenos Bacterianos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Sci Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido