Asymmetric Cryo-EM Structure of Anthrax Toxin Protective Antigen Pore with Lethal Factor N-Terminal Domain
| Autor: | Edward P. Gogol, Alexandra J Machen, Yifei Qi, Srayanta Mukherjee, Tommi A. White, Rebecca Dillard, Caleb Trecazzi, Wonpil Im, Pierce T. O’Neil, Narahari Akkaladevi, Mark T. Fisher |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cryo-electron microscopy cryoSPARC Health Toxicology and Mutagenesis Anthrax toxin Bacterial Toxins translocation lcsh:Medicine Molecular Dynamics Simulation Biology Toxicology anthrax toxin lethal factor protective antigen pore formation nanodisc cryo-EM Article Anthrax 03 medical and health sciences Lethal toxin Nanodisc Antigens Bacterial 030102 biochemistry & molecular biology Cryoelectron Microscopy lcsh:R Protein Structure Tertiary Lethal factor Crystallography 030104 developmental biology Protective antigen Solubilization Biophysics Anthrax toxin protective antigen |
| Zdroj: | Toxins, Vol 9, Iss 10, p 298 (2017) Toxins Toxins; Volume 9; Issue 10; Pages: 298 |
| ISSN: | 2072-6651 |
| Popis: | The anthrax lethal toxin consists of protective antigen (PA) and lethal factor (LF). Understanding both the PA pore formation and LF translocation through the PA pore is crucial to mitigating and perhaps preventing anthrax disease. To better understand the interactions of the LF-PA engagement complex, the structure of the LFN-bound PA pore solubilized by a lipid nanodisc was examined using cryo-EM. CryoSPARC was used to rapidly sort particle populations of a heterogeneous sample preparation without imposing symmetry, resulting in a refined 17 Å PA pore structure with 3 LFN bound. At pH 7.5, the contributions from the three unstructured LFN lysine-rich tail regions do not occlude the Phe clamp opening. The open Phe clamp suggests that, in this translocation-compromised pH environment, the lysine-rich tails remain flexible and do not interact with the pore lumen region. |
| Databáze: | OpenAIRE |
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