| Full text | |
| Author(s): |
Fernandes, Carlos A. H.
;
Pazin, Wallance M.
;
Dreyer, Thiago R.
;
Bicev, Renata N.
;
Cavalcante, Walter L. G.
;
Fortes-Dias, Consuelo L.
;
Ito, Amando S.
;
Oliveira, Cristiano L. P.
;
Fernandez, Roberto Morato
;
Fontes, Marcos R. M.
Total Authors: 10
|
| Document type: | Journal article |
| Source: | SCIENTIFIC REPORTS; v. 7, MAR 3 2017. |
| Web of Science Citations: | 9 |
| Abstract | |
Crotoxin (CTX) is the main neurotoxin found in Crotalus durissus rattlesnake venoms being composed by a nontoxic and non-enzymatic component (CA) and a toxic phospholipase A(2) (CB). Previous crystallographic structures of CTX and CB provided relevant insights: (i) CTX structure showed a 1:1 molecular ratio between CA and CB, presenting three tryptophan residues in the CA/CB interface and one exposed to solvent; (ii) CB structure displayed a tetrameric conformation. This study aims to provide further information on the CTX mechanism of action by several biophysical methods. Our data show that isolated CB can in fact form tetramers in solution; however, these tetramers can be dissociated by CA titration. Furthermore, CTX exhibits a strong reduction in fluorescence intensity and lifetime compared with isolated CA and CB, suggesting that all tryptophan residues in CTX may be hidden by the CA/CB interface. By companying spectroscopy fluorescence and SAXS data, we obtained a new structural model for the CTX heterodimer in which all tryptophans are located in the interface, and the N-terminal region of CB is largely exposed to the solvent. Based on this model, we propose a toxic mechanism of action for CTX, involving the interaction of N-terminal region of CB with the target before CA dissociation. (AU) | |
| FAPESP's process: | 15/17286-0 - Structural and functional studies aiming to understand the role of snake venoms toxins and how to inhibit their biological activity |
| Grantee: | Marcos Roberto de Mattos Fontes |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/17864-8 - Structural Studies with Neurotoxic Phospholipases A2. |
| Grantee: | Carlos Alexandre Henrique Fernandes |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |