Structural highlights
Function
[PAG_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax. [CYAA_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. EF is a calmodulin-dependent adenylyl cyclase that, when associated with PA, causes edema. EF is not toxic by itself and it is required for the survival of germinated spores within macrophages at the early stages of infection. Provokes dramatic elevation of intracellular cAMP levels in the host.
Publication Abstract from PubMed
Following assembly, the anthrax protective antigen (PA) forms an oligomeric translocon that unfolds and translocates either its lethal factor (LF) or edema factor (EF) into the host cell. Here, we report the cryo-EM structures of heptameric PA channels with partially unfolded LF and EF at 4.6 and 3.1-A resolution, respectively. The first alpha helix and beta strand of LF and EF unfold and dock into a deep amphipathic cleft, called the alpha clamp, which resides at the interface of two PA monomers. The alpha-clamp-helix interactions exhibit structural plasticity when comparing the structures of lethal and edema toxins. EF undergoes a largescale conformational rearrangement when forming the complex with the channel. A critical loop in the PA binding interface is displaced for about 4 A, leading to the weakening of the binding interface prior to translocation. These structures provide key insights into the molecular mechanisms of translocation-coupled protein unfolding and translocation.
Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors.,Hardenbrook NJ, Liu S, Zhou K, Ghosal K, Hong Zhou Z, Krantz BA Nat Commun. 2020 Feb 11;11(1):840. doi: 10.1038/s41467-020-14658-6. PMID:32047164[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hardenbrook NJ, Liu S, Zhou K, Ghosal K, Hong Zhou Z, Krantz BA. Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors. Nat Commun. 2020 Feb 11;11(1):840. doi: 10.1038/s41467-020-14658-6. PMID:32047164 doi:http://dx.doi.org/10.1038/s41467-020-14658-6
