Insights on the structure of native CNF, an endogenous phospholipase A2 inhibitor from Crotalus durissus terrificus, the South American rattlesnake
| Autor: | Wallance Moreira Pazin, Mario de Oliveira Neto, Lutiana Amaral de Melo, Marcos R.M. Fontes, Kelli Roberta Lobo, Roberto M. Fernandez, Paula Ladeira Ortolani, Carlos A.H. Fernandes, Consuelo Latorre Fortes-Dias, Márcia Helena Borges |
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| Rok vydání: | 2014 |
| Předmět: |
Phospholipase A2 Inhibitors
Molecular Sequence Data Biophysics Venom Reptilian Proteins Biochemistry Protein Structure Secondary Analytical Chemistry Phospholipase A2 X-Ray Diffraction Tetramer Scattering Small Angle Animals Homomeric South American rattlesnake Amino Acid Sequence Protein Structure Quaternary Molecular Biology Glycoproteins Phospholipase A Sequence Homology Amino Acid biology Crotalus South America Crotoxin biology.organism_classification Protein Structure Tertiary Phospholipases A2 Chromatography Gel biology.protein Tyrosine Protein quaternary structure Protein Multimerization |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1844:1569-1579 |
| ISSN: | 1570-9639 |
| Popis: | Several snake species possess endogenous phospholipase A2 inhibitors (sbPLIs) in their blood plasma, the primary role of which is protection against an eventual presence of toxic phospholipase A2 (PLA2) from their venom glands in the circulation. These inhibitors have an oligomeric structure of, at least, three subunits and have been categorized into three classes (α, β and γ) based on their structural features. SbγPLIs have been further subdivided into two subclasses according to their hetero or homomeric nature, respectively. Despite the considerable number of sbγPLIs described, their structures and mechanisms of action are still not fully understood. In the present study, we focused on the native structure of CNF, a homomeric sbγPLI from Crotalus durissus terrificus, the South American rattlesnake. Based on the results of different biochemical and biophysical experiments, we concluded that, while the native inhibitor occurs as a mixture of oligomers, tetrameric arrangement appears to be the predominant quaternary structure. The inhibitory activity of CNF is most likely associated with this oligomeric conformation. In addition, we suggest that the CNF tetramer has a spherical shape and that tyrosinyl residues could play an important role in the oligomerization. The carbohydrate moiety, which is present in most sbγPLIs, is not essential for the inhibitory activity, oligomerization or complex formation of the CNF with the target PLA2. A minor component, comprising no more than 16% of the sample, was identified in the CNF preparations. The amino-terminal sequence of that component is similar to the B subunits of the heteromeric sbγPLIs; however, the role played by such molecule in the functionality of the CNF, if any, remains to be determined. |
| Databáze: | OpenAIRE |
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