6qbl

NMR Structure of Big-defensin 1 from oyster Crassostrea gigas

spinqualitylabelsall models 6qbl Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qbl is a 1 chain structure with sequence from Crassostrea gigas. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 10 models Ligands: AAR, PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F6M2J2_MAGGI Publication Abstract from PubMed Big defensins, ancestors of beta-defensins, are composed of a beta-defensin-like C-terminal domain and a globular hydrophobic ancestral N-terminal domain. This unique structure is found in a limited number of phylogenetically distant species, including mollusks, ancestral chelicerates, and early-branching cephalochordates, mostly living in marine environments. One puzzling evolutionary issue concerns the advantage for these species of having maintained a hydrophobic domain lost during evolution toward beta-defensins. Using native ligation chemistry, we produced the oyster Crassostrea gigas BigDef1 (Cg-BigDef1) and its separate domains. Cg-BigDef1 showed salt-stable and broad-range bactericidal activity, including against multidrug-resistant human clinical isolates of Staphylococcus aureus We found that the ancestral N-terminal domain confers salt-stable antimicrobial activity to the beta-defensin-like domain, which is otherwise inactive. Moreover, upon contact with bacteria, the N-terminal domain drives Cg-BigDef1 assembly into nanonets that entrap and kill bacteria. We speculate that the hydrophobic N-terminal domain of big defensins has been retained in marine phyla to confer salt-stable interactions with bacterial membranes in environments where electrostatic interactions are impaired. Those remarkable properties open the way to future drug developments when physiological salt concentrations inhibit the antimicrobial activity of vertebrate beta-defensins.IMPORTANCE beta-Defensins are host defense peptides controlling infections in species ranging from humans to invertebrates. However, the antimicrobial activity of most human beta-defensins is impaired at physiological salt concentrations. We explored the properties of big defensins, the beta-defensin ancestors, which have been conserved in a number of marine organisms, mainly mollusks. By focusing on a big defensin from oyster (Cg-BigDef1), we showed that the N-terminal domain lost during evolution toward beta-defensins confers bactericidal activity to Cg-BigDef1, even at high salt concentrations. Cg-BigDef1 killed multidrug-resistant human clinical isolates of Staphylococcus aureus Moreover, the ancestral N-terminal domain drove the assembly of the big defensin into nanonets in which bacteria are entrapped and killed. This discovery may explain why the ancestral N-terminal domain has been maintained in diverse marine phyla and creates a new path of discovery to design beta-defensin derivatives active at physiological and high salt concentrations. The Ancestral N-Terminal Domain of Big Defensins Drives Bacterially Triggered Assembly into Antimicrobial Nanonets.,Loth K, Vergnes A, Barreto C, Voisin SN, Meudal H, Da Silva J, Bressan A, Belmadi N, Bachere E, Aucagne V, Cazevielle C, Marchandin H, Rosa RD, Bulet P, Touqui L, Delmas AF, Destoumieux-Garzon D MBio. 2019 Oct 22;10(5). pii: mBio.01821-19. doi: 10.1128/mBio.01821-19. PMID:31641083 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Defensin 3D structures

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