This is not the latest version of this item. The latest version can be found at: https://www.research-collection.ethz.ch/handle/20.500.11850/301619
Pilpa, Rosemarie M.
Marlett, John M.
Young, John A.T.
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
Cellular receptors can act as molecular switches, regulating the sensitivity of microbial proteins to conformational changes that promote cellular entry. The activities of these receptor-based switches are only partially understood. In this paper, we sought to understand the mechanism that underlies the activity of the ANTXR2 anthrax toxin receptor-based switch that binds to domains 2 and 4 of the protective antigen (PA) toxin subunit. Receptor-binding restricts structural changes within the heptameric PA prepore that are required for pore conversion to an acidic endosomal compartment. The transfer cross-saturation (TCS) NMR approach was used to monitor changes in the heptameric PA-receptor contacts at different steps during prepore-to-pore conversion. These studies demonstrated that receptor contact with PA domain 2 is weakened prior to pore conversion, defining a novel intermediate in this pathway. Importantly, ANTXR2 remained bound to PA domain 4 following pore conversion, suggesting that the bound receptor might influence the structure and/or function of the newly formed pore. These studies provide new insights into the function of a receptor-based molecular switch that controls anthrax toxin entry into cells Show more
Journal / seriesPLoS Pathogens
Pages / Article No.
PublisherPublic Library of Science
Organisational unit03782 - Riek, Roland / Riek, Roland
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