6QBK
NMR Structure of Big-defensin 1 [44-93] from oyster Crassostrea gigas
Summary for 6QBK
| Entry DOI | 10.2210/pdb6qbk/pdb |
| NMR Information | BMRB: 34345 |
| Descriptor | Big defensin 1 (1 entity in total) |
| Functional Keywords | big-defensin, antimicrobial, marine, oyster, antimicrobial protein |
| Biological source | Crassostrea gigas (Pacific oyster) |
| Total number of polymer chains | 1 |
| Total formula weight | 6011.60 |
| Authors | Loth, K.,Meudal, H.,Delmas, A.F. (deposition date: 2018-12-21, release date: 2019-12-11, Last modification date: 2023-06-14) |
| Primary citation | Loth, K.,Vergnes, A.,Barreto, C.,Voisin, S.N.,Meudal, H.,Da Silva, J.,Bressan, A.,Belmadi, N.,Bachere, E.,Aucagne, V.,Cazevielle, C.,Marchandin, H.,Rosa, R.D.,Bulet, P.,Touqui, L.,Delmas, A.F.,Destoumieux-Garzon, D. The Ancestral N-Terminal Domain of Big Defensins Drives Bacterially Triggered Assembly into Antimicrobial Nanonets. Mbio, 10:-, 2019 Cited by PubMed Abstract: Big defensins, ancestors of β-defensins, are composed of a β-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 β-defensins. Using native ligation chemistry, we produced the oyster BigDef1 (BigDef1) and its separate domains. BigDef1 showed salt-stable and broad-range bactericidal activity, including against multidrug-resistant human clinical isolates of We found that the ancestral N-terminal domain confers salt-stable antimicrobial activity to the β-defensin-like domain, which is otherwise inactive. Moreover, upon contact with bacteria, the N-terminal domain drives 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 β-defensins. β-Defensins are host defense peptides controlling infections in species ranging from humans to invertebrates. However, the antimicrobial activity of most human β-defensins is impaired at physiological salt concentrations. We explored the properties of big defensins, the β-defensin ancestors, which have been conserved in a number of marine organisms, mainly mollusks. By focusing on a big defensin from oyster (BigDef1), we showed that the N-terminal domain lost during evolution toward β-defensins confers bactericidal activity to BigDef1, even at high salt concentrations. BigDef1 killed multidrug-resistant human clinical isolates of 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 β-defensin derivatives active at physiological and high salt concentrations. PubMed: 31641083DOI: 10.1128/mBio.01821-19 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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