This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anthrax is caused by one of the two virulence factors produced by the bacteria Bacillus anthracis. This factor is a cocktail of three monomeric proteins, lethal factor (LF, 90kD), edema factor (EF, 89kD) and the protective antigen (PA, 83kD). Understanding the molecular recognition processes involved in the formation of the toxic Antrahx complex and the eventual delivery of the lethal and edema factors is critical to gaining insight into the pathogenesis of anthrax, and eventually to rational design of agents to block toxin action. Toward this end, we had directly visualized the PA63h.LF complex from analysis of images of specimens suspended in vitrified buffer by cryo-electron microscopy (Ren et al., 2004). Comparison of the averaged 3-dimensional (3-D) views of the liganded and unliganded complex showed that the PA63h molecule binds to one LF molecule, which is localized to the non-membrane-interacting ?top? face of the heptamer. The observed asymmetric binding of the ligand involves interaction with successive (at least 3) PA63 monomers and causes partial unravelling of the heptamer enlarging the lumen volume (Ren et al., 2004). This structural perturbation could be utilized to allow the ligand to ease into the vestibular lumen prior to its eventual translocation through the pore in the membrane.
| Salmon, Loïc; Ahlstrom, Logan S; Horowitz, Scott et al. (2016) Capturing a Dynamic Chaperone-Substrate Interaction Using NMR-Informed Molecular Modeling. J Am Chem Soc 138:9826-39 |
| Bruno, Paul A; Morriss-Andrews, Alex; Henderson, Andrew R et al. (2016) A Synthetic Loop Replacement Peptide That Blocks Canonical NF-?B Signaling. Angew Chem Int Ed Engl 55:14997-15001 |
| Montiel-García, Daniel J; Mannige, Ranjan V; Reddy, Vijay S et al. (2016) Structure based sequence analysis of viral and cellular protein assemblies. J Struct Biol 196:299-308 |
| Rosen, Laura E; Kathuria, Sagar V; Matthews, C Robert et al. (2015) Non-native structure appears in microseconds during the folding of E. coli RNase H. J Mol Biol 427:443-53 |
| Cheng, Shanshan; Brooks 3rd, Charles L (2015) Protein-Protein Interfaces in Viral Capsids Are Structurally Unique. J Mol Biol 427:3613-3624 |
| Carrillo-Tripp, Mauricio; Montiel-García, Daniel Jorge; Brooks 3rd, Charles L et al. (2015) CapsidMaps: protein-protein interaction pattern discovery platform for the structural analysis of virus capsids using Google Maps. J Struct Biol 190:47-55 |
| Ahlstrom, Logan S; Law, Sean M; Dickson, Alex et al. (2015) Multiscale modeling of a conditionally disordered pH-sensing chaperone. J Mol Biol 427:1670-80 |
| Taylor, Kenneth A; Feig, Michael; Brooks 3rd, Charles L et al. (2014) Role of the essential light chain in the activation of smooth muscle myosin by regulatory light chain phosphorylation. J Struct Biol 185:375-82 |
| Zeng, Xiancheng; Chugh, Jeetender; Casiano-Negroni, Anette et al. (2014) Flipping of the ribosomal A-site adenines provides a basis for tRNA selection. J Mol Biol 426:3201-3213 |
| Vashisth, Harish; Skiniotis, Georgios; Brooks 3rd, Charles Lee (2014) Collective variable approaches for single molecule flexible fitting and enhanced sampling. Chem Rev 114:3353-65 |
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