dSarm / Sarm 1 Is Required for Activation of an Injury - Induced Axon Death Pathway

Immun. 65, 2396 (1997). 7. N. H. Salzman, D. Ghosh, K. M. Huttner, Y. Paterson, C. L. Bevins, Nature 422, 522 (2003). 8. B. Ericksen, Z. Wu, W. Lu, R. I. Lehrer, Antimicrob. Agents Chemother. 49, 269 (2005). 9. N. H. Salzman et al., Nat. Immunol. 11, 76 (2010). 10. See supplementary materials on Science Online. 11. A. J. Bäumler, R. M. Tsolis, P. J. Valentine, T. A. Ficht, F. Heffron, Infect. Immun. 65, 2254 (1997). 12. P. Cossart, P. J. Sansonetti, Science 304, 242 (2004). 13. G. Wei et al., J. Biol. Chem. 285, 16275 (2010). 14. C. P. Hill, J. Yee, M. E. Selsted, D. Eisenberg, Science 251, 1481 (1991). 15. A. Szyk et al., Protein Sci. 15, 2749 (2006). 16. G. Wei et al., J. Biol. Chem. 284, 29180 (2009). 17. More precisely, the imidazole side chain of His of both monomer b and d interacts with the C-terminal carboxyl group of Leu in monomers c and a, respectively, and two backbone-backbone H-bonds form between Ala N of monomers a and c and Cys6 O of monomers d and b (Fig. 3A and fig. S12). 18. Furthermore, H27W-HD6 does not form the two reciprocal main-chain H-bonds donated by Ala of one dimer to Cys of the other. Consequently, monomers b and d of H27W-HD6 “spring loose” from monomers a and c, and the resultant mutant tetramer becomes vertically more extended and laterally more flattened than that of wild-type HD6 (Fig. 3B). The extended and flattened H27W tetramer is less stable than its “twisted” wild-type counterpart because of reduced hydrophobic packing and the lost interdimer interactions (fig. S14). Overall, the crystal structures of both defensins suggest that His plays an important role in stabilizing HD6 tetramer stabilization and likely contributes to an elongated high-order assembly of HD6 molecules by accentuating a propagating twist within and beyond the tetramer structure. The assembled HD6 structure shown is bowed when viewed from one perspective and linear when rotated by 90° (fig. S12). This bowing, along with coalescence of fibrils extending from different anchoring points on the bacterial surface, might account for the branching and netlike formation evident in the scanning electron micrographs that appear in the figures. 19. K. Brandl, G. Plitas, B. Schnabl, R. P. DeMatteo, E. G. Pamer, J. Exp. Med. 204, 1891 (2007). 20. R. I. Lehrer et al., J. Immunol. 183, 480 (2009). 21. H. L. Andrews-Polymenis, A. J. Bäumler, B. A. McCormick, F. C. Fang, Infect. Immun. 78, 2356 (2010). 22. T. Ayabe et al., Nat. Immunol. 1, 113 (2000). 23. D. Ghosh et al., Nat. Immunol. 3, 583 (2002). 24. M. T. Shanahan, H. Tanabe, A. J. Ouellette, Infect. Immun. 79, 459 (2011).