A Receptor-based Switch that Regulates Anthrax Toxin Pore Formation

PLoS Pathogens

John M. Marlett¹  Rosemarie M. Pilpa²  Roland Riek²  John A. T. Young³  Monika Bayrhuber³ 

[1] Laboratory of Physical Chemistry, ETH Zürich, Zürich, Switzerland;Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, California, United States of America;Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America

关键词: Toxins;    Anthrax;    Gel filtration;    Signal to noise ratio;    Amides;    Co-immunoprecipitation;    Intoxication;    Receptor physiology;   

DOI  :  10.1371/journal.ppat.1002354

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY