Site-Specific Labeling and (19)F NMR Provide Direct Evidence for Dynamic Behavior of the Anthrax Toxin Pore ϕ-Clamp Structure
| Autor: | James G. Bann, William M. Westler, Masaru Miyagi, Srinivas Gonti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Antigens Bacterial Protein Folding 0303 health sciences Host cell cytosol Protein Conformation Direct evidence Chemistry Anthrax toxin Bacterial Toxins 030302 biochemistry & molecular biology Cell Fluorine-19 NMR Biochemistry Article Fluorine-19 Magnetic Resonance Imaging 03 medical and health sciences Residue (chemistry) Cytosol medicine.anatomical_structure medicine Biophysics Nuclear Magnetic Resonance Biomolecular Binding domain |
| Zdroj: | Biochemistry |
| Popis: | The anthrax toxin protective antigen (PA), the membrane binding and pore-forming component of the anthrax toxin, was studied using (19)F NMR. We site-specifically labeled PA with p-fluorophenylalanine (pF-Phe) at Phe427, a critically important residue that comprises the ϕ-clamp that is required for translocation of edema factor (EF) and lethal factor (LF) into the host cell cytosol. We utilized (19)F NMR to follow low-pH-induced structural changes in the prepore, alone and bound to the N-terminal PA binding domain of LF, LF(N). Our studies indicate that pF-Phe427 is dynamic in the prepore state and then becomes more dynamic in the transition to the pore. An increase in dynamic behavior at the ϕ-clamp may provide the necessary room for movement needed in translocating EF and LF into the cell cytosol. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|