A Receptor-based Switch That Regulates Anthrax Toxin Pore Formation

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2011 Dec 17

PMID 22174672

Citations 22

Authors

Rosemarie M Pilpa

Monika Bayrhuber

John M Marlett

Roland Riek

John A T Young

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Assembly and Function of the Anthrax Toxin Protein Translocation Complex.

Liddington R Subcell Biochem. 2020; 96:563-577.

PMID: 33252744 DOI: 10.1007/978-3-030-58971-4_18.

Exploring the Nature of Cationic Blocker Recognition by the Anthrax Toxin Channel.

Momben Abolfath S, Kolberg M, Karginov V, Leppla S, Nestorovich E Biophys J. 2019; 117(9):1751-1763.

PMID: 31587826 PMC: 6838753. DOI: 10.1016/j.bpj.2019.08.041.

Human monoclonal anti-protective antigen antibody for the low-dose post-exposure prophylaxis and treatment of Anthrax.

Tang Q, Xiong S, Liang X, Kuai X, Wang Y, Wang C BMC Infect Dis. 2018; 18(1):640.

PMID: 30526504 PMC: 6288905. DOI: 10.1186/s12879-018-3542-6.

Effect of late endosomal DOBMP lipid and traditional model lipids of electrophysiology on the anthrax toxin channel activity.

Kalu N, Atsmon-Raz Y, Momben Abolfath S, Lucas L, Kenney C, Leppla S Biochim Biophys Acta Biomembr. 2018; 1860(11):2192-2203.

PMID: 30409515 PMC: 6814629. DOI: 10.1016/j.bbamem.2018.08.011.

Effect of endosomal acidification on small ion transport through the anthrax toxin PA channel.

Kalu N, Alcaraz A, Yamini G, Momben Abolfath S, Lucas L, Kenney C FEBS Lett. 2017; 591(21):3481-3492.

PMID: 28963849 PMC: 5683923. DOI: 10.1002/1873-3468.12866.

References

Leppla S . Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc Natl Acad Sci U S A. 1982; 79(10):3162-6. PMC: 346374. DOI: 10.1073/pnas.79.10.3162. View

Lacy D, Wigelsworth D, Melnyk R, Harrison S, Collier R . Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation. Proc Natl Acad Sci U S A. 2004; 101(36):13147-51. PMC: 516539. DOI: 10.1073/pnas.0405405101. View

Xu Q, Hesek E, Zeng M . Transcriptional stimulation of anthrax toxin receptors by anthrax edema toxin and Bacillus anthracis Sterne spore. Microb Pathog. 2007; 43(1):37-45. PMC: 1973154. DOI: 10.1016/j.micpath.2007.03.002. View

Takahashi H, Nakanishi T, Kami K, Arata Y, Shimada I . A novel NMR method for determining the interfaces of large protein-protein complexes. Nat Struct Biol. 2000; 7(3):220-3. DOI: 10.1038/73331. View

Nakanishi T, Miyazawa M, Sakakura M, Terasawa H, Takahashi H, Shimada I . Determination of the interface of a large protein complex by transferred cross-saturation measurements. J Mol Biol. 2002; 318(2):245-9. DOI: 10.1016/S0022-2836(02)00018-9. View

Vitale G, Pellizzari R, Recchi C, Napolitani G, Mock M, Montecucco C . Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Commun. 1998; 248(3):706-11. DOI: 10.1006/bbrc.1998.9040. View

Maxfield F, McGraw T . Endocytic recycling. Nat Rev Mol Cell Biol. 2004; 5(2):121-32. DOI: 10.1038/nrm1315. View

Finzi A, Xiang S, Pacheco B, Wang L, Haight J, Kassa A . Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol Cell. 2010; 37(5):656-67. PMC: 2854584. DOI: 10.1016/j.molcel.2010.02.012. View

Scobie H, Rainey G, Bradley K, Young J . Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci U S A. 2003; 100(9):5170-4. PMC: 154317. DOI: 10.1073/pnas.0431098100. View

10.

Schrodel A, de Marco A . Characterization of the aggregates formed during recombinant protein expression in bacteria. BMC Biochem. 2005; 6:10. PMC: 1175841. DOI: 10.1186/1471-2091-6-10. View

11.

Duesbery N, Webb C, Leppla S, Gordon V, Klimpel K, Copeland T . Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science. 1998; 280(5364):734-7. DOI: 10.1126/science.280.5364.734. View

12.

Masse J, Keller R . AutoLink: automated sequential resonance assignment of biopolymers from NMR data by relative-hypothesis-prioritization-based simulated logic. J Magn Reson. 2005; 174(1):133-51. DOI: 10.1016/j.jmr.2005.01.017. View

13.

Scobie H, Marlett J, Rainey G, Lacy D, Collier R, Young J . Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation. PLoS One. 2007; 2(3):e329. PMC: 1824706. DOI: 10.1371/journal.pone.0000329. View

14.

Martchenko M, Jeong S, Cohen S . Heterodimeric integrin complexes containing beta1-integrin promote internalization and lethality of anthrax toxin. Proc Natl Acad Sci U S A. 2010; 107(35):15583-8. PMC: 2932583. DOI: 10.1073/pnas.1010145107. View

15.

Katayama H, Janowiak B, Brzozowski M, Juryck J, Falke S, Gogol E . GroEL as a molecular scaffold for structural analysis of the anthrax toxin pore. Nat Struct Mol Biol. 2008; 15(7):754-60. PMC: 2504863. DOI: 10.1038/nsmb.1442. View

16.

Sun J, Collier R . Disulfide bonds in the ectodomain of anthrax toxin receptor 2 are required for the receptor-bound protective-antigen pore to function. PLoS One. 2010; 5(5):e10553. PMC: 2866654. DOI: 10.1371/journal.pone.0010553. View

17.

Roostaee A, Cote S, Roucou X . Aggregation and amyloid fibril formation induced by chemical dimerization of recombinant prion protein in physiological-like conditions. J Biol Chem. 2009; 284(45):30907-16. PMC: 2781490. DOI: 10.1074/jbc.M109.057950. View

18.

Petosa C, Collier R, Klimpel K, Leppla S, Liddington R . Crystal structure of the anthrax toxin protective antigen. Nature. 1997; 385(6619):833-8. DOI: 10.1038/385833a0. View

19.

Petit C, Zhang J, Sapienza P, Fuentes E, Lee A . Hidden dynamic allostery in a PDZ domain. Proc Natl Acad Sci U S A. 2009; 106(43):18249-54. PMC: 2775317. DOI: 10.1073/pnas.0904492106. View

20.

Navaratnarajah C, Oezguen N, Rupp L, Kay L, Leonard V, Braun W . The heads of the measles virus attachment protein move to transmit the fusion-triggering signal. Nat Struct Mol Biol. 2011; 18(2):128-34. PMC: 3059746. DOI: 10.1038/nsmb.1967. View