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.
Vyšlo v časopise: A Receptor-based Switch that Regulates Anthrax Toxin Pore Formation. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002354 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002354
1. CoteMZhengYMLiuSL 2009 Receptor binding and low pH coactivate oncogenic retrovirus envelope-mediated fusion. J Virol 83 11447 11455
2. MelikyanGBBarnardRJAbrahamyanLGMothesWYoungJA 2005 Imaging individual retroviral fusion events: from hemifusion to pore formation and growth. Proc Natl Acad Sci U S A 102 8728 8733
3. FinziAXiangSHPachecoBWangLHaightJ 2010 Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol Cell 37 656 667
4. NavaratnarajahCKOezguenNRuppLKayLLeonardVH 2011 The heads of the measles virus attachment protein move to transmit the fusion-triggering signal. Nat Struct Mol Biol 18 128 134
5. ConnollySAJacksonJOJardetzkyTSLongneckerR 2011 Fusing structure and function: a structural view of the herpesvirus entry machinery. Nat Rev Microbiol 9 369 381
6. VitaleGPellizzariRRecchiCNapolitaniGMockM 1998 Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Commun 248 706 711
7. LepplaSH 1982 Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc Natl Acad Sci U S A 79 3162 3166
8. DuesberyNSWebbCPLepplaSHGordonVMKlimpelKR 1998 Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280 734 737
9. MartchenkoMJeongSYCohenSN 2010 Heterodimeric integrin complexes containing beta1-integrin promote internalization and lethality of anthrax toxin. Proc Natl Acad Sci U S A 107 15583 15588
10. ScobieHMRaineyGJBradleyKAYoungJA 2003 Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci U S A 100 5170 5174
11. BradleyKAMogridgeJMourezMCollierRJYoungJA 2001 Identification of the cellular receptor for anthrax toxin. Nature 414 225 229
12. ScobieHMWigelsworthDJMarlettJMThomasDRaineyGJ 2006 Anthrax toxin receptor 2-dependent lethal toxin killing in vivo. PLoS Pathog 2 e111
13. XuQHesekEDZengM 2007 Transcriptional stimulation of anthrax toxin receptors by anthrax edema toxin and Bacillus anthracis Sterne spore. Microb Pathog 43 37 45
14. LiuSCrownDMiller-RandolphSMoayeriMWangH 2009 Capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo. Proc Natl Acad Sci U S A 106 12424 12429
15. LacyDBWigelsworthDJMelnykRAHarrisonSCCollierRJ 2004 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 101 13147 13151
16. SantelliEBankstonLALepplaSHLiddingtonRC 2004 Crystal structure of a complex between anthrax toxin and its host cell receptor. Nature 430 905 908
17. KintzerAFThorenKLSterlingHJDongKCFeldGK 2009 The protective antigen component of anthrax toxin forms functional octameric complexes. J Mol Biol 392 614 629
18. PetosaCCollierRJKlimpelKRLepplaSHLiddingtonRC 1997 Crystal structure of the anthrax toxin protective antigen. Nature 385 833 838
19. AbramiLLepplaSHvan der GootFG 2006 Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis. J Cell Biol 172 309 320
20. AbramiLLiuSCossonPLepplaSHvan der GootFG 2003 Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process. J Cell Biol 160 321 328
21. YoungJACollierRJ 2007 Anthrax toxin: receptor binding, internalization, pore formation, and translocation. Annu Rev Biochem 76 243 265
22. ScobieHMMarlettJMRaineyGJLacyDBCollierRJ 2007 Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation. PLoS ONE 2 e329
23. RaineyGJWigelsworthDJRyanPLScobieHMCollierRJ 2005 Receptor-specific requirements for anthrax toxin delivery into cells. Proc Natl Acad Sci U S A 102 13278 13283
24. WimalasenaDSJanowiakBELovellSMiyagiMSunJ 2010 Evidence that histidine protonation of receptor-bound anthrax protective antigen is a trigger for pore formation. Biochemistry 49 6973 6983
25. RajapakshaMEichlerJFHajduchJAndersonDEKirkKL 2009 Monitoring anthrax toxin receptor dissociation from the protective antigen by NMR. Protein Sci 18 17 23
26. AbramiLBischofbergerMKunzBGrouxRvan der GootFG 2010 Endocytosis of the anthrax toxin is mediated by clathrin, actin and unconventional adaptors. PLoS Pathog 6 e1000792
27. WilliamsASLovellSAnbanandamAEl-ChamiRBannJG 2009 Domain 4 of the anthrax protective antigen maintains structure and binding to the host receptor CMG2 at low pH. Protein Sci 18 2277 2286
28. WolfeJTKrantzBARaineyGJYoungJACollierRJ 2005 Whole-cell voltage clamp measurements of anthrax toxin pore current. J Biol Chem 280 39417 39422
29. GaoMSchultenK 2006 Onset of anthrax toxin pore formation. Biophys J 90 3267 3279
30. PellecchiaM 2005 Solution nuclear magnetic resonance spectroscopy techniques for probing intermolecular interactions. Chem Biol 12 961 971
31. NishidaNSumikawaHSakakuraMShimbaNTakahashiH 2003 Collagen-binding mode of vWF-A3 domain determined by a transferred cross-saturation experiment. Nat Struct Biol 10 53 58
32. TakahashiHNakanishiTKamiKArataYShimadaI 2000 A novel NMR method for determining the interfaces of large protein-protein complexes. Nat Struct Biol 7 220 223
33. NakanishiTMiyazawaMSakakuraMTerasawaHTakahashiH 2002 Determination of the interface of a large protein complex by transferred cross-saturation measurements. J Mol Biol 318 245 249
34. DelaglioFGrzesiekSVuisterGWZhuGPfeiferJ 1995 NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6 277 293
35. MasseJEKellerR 2005 AutoLink: automated sequential resonance assignment of biopolymers from NMR data by relative-hypothesis-prioritization-based simulated logic. J Magn Reson 174 133 151
36. GoddardTDKDG 2006 Sparky 3. University of California, San Francisco
37. ShimadaIUedaTMatsumotoMSakakuraMOsawaM 2009 Cross-saturation and transferred cross-saturation experiments. Prog Nucl Magn Reson Spectrosc 54 123 140
38. GardnerKHKayLE 1998 The use of 2H, 13C, 15N multidimensional NMR to study the structure and dynamics of proteins. Annu Rev Biophys Biomol Struct 27 357 406
39. MaxfieldFRMcGrawTE 2004 Endocytic recycling. Nat Rev Mol Cell Biol 5 121 132
40. PetitCMZhangJSapienzaPJFuentesEJLeeAL 2009 Hidden dynamic allostery in a PDZ domain. Proc Natl Acad Sci U S A 106 18249 18254
41. HsuCHPanYRLiaoYDWuSHChenC 2010 NMR and biophysical elucidation of structural effects on extra N-terminal methionine residue of recombinant amphibian RNases from Rana catesbeiana. J Biochem 148 209 215
42. GoddardTDKnellerDG 2005 Characterization of the aggregates formed during recombinant protein expression in bacteria. BMC Biochem 6 10
43. RoostaeeACoteSRoucouX 2009 Aggregation and amyloid fibril formation induced by chemical dimerization of recombinant prion protein in physiological-like conditions. J Biol Chem 284 30907 30916
44. GouauxEHobaughMSongL 1997 alpha-Hemolysin, gamma-hemolysin, and leukocidin from Staphylococcus aureus: distant in sequence but similar in structure. Protein Sci 6 2631 2635
45. KatayamaHJanowiakBEBrzozowskiMJuryckJFalkeS 2008 GroEL as a molecular scaffold for structural analysis of the anthrax toxin pore. Nat Struct Mol Biol 15 754 60
46. SunJCollierRJ 2010 Disulfide bonds in the ectodomain of anthrax toxin receptor 2 are required for the receptor-bound protective-antigen pore to function. PLoS One 5 e10553
47. LacyDBWigelsworthDJScobieHMYoungJACollierRJ 2004 Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor. Proc Natl Acad Sci U S A 101 6367 6372
48. ScobieHMThomasDMarlettJMDestitoGWigelsworthDJ 2005 A soluble receptor decoy protects rats against anthrax lethal toxin challenge. J Infect Dis 192 1047 1051
49. MillerCJElliottJLCollierRJ 1999 Anthrax protective antigen: prepore-to-pore conversion. Biochemistry 38 10432 10441
50. KupceEWagnerG 1996 Multisite band-selective decoupling in proteins. J Magn Reson B 110 309 312
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