Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10537980 | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | 2005 | 10 Pages |
Abstract
LVP1, a novel protein inducing lipolytic response in adipose cells, was purified from scorpion Buthus occitanus tunetanus venom. It represented 1% of crude venom proteins, with pHiâ¼6 and molecular mass of 16 170 Da. In contrast to well-characterized scorpion toxins, reduction and alkylation of LVP1 revealed an heterodimeric structure. Isolated α and β chains of LVP1 have a respective molecular mass of 8877 and 8807 Da as determined by mass spectrometry. The N-terminal and some internal peptide sequences of LVP1α and β were determined by Edman degradation. The full amino acid sequences of both chains were deduced from nucleotide sequences of the corresponding cDNAs prepared based on peptide sequences and the 3â² and 5â² RACE methodologies. LVP1α and β cDNAs encode a signal peptide of 22 residues and a mature peptide of 69 and 73 residues, respectively. Each mature peptide contains seven cysteines, which are compatible with an interchain disulfide bridge. The cDNA deduced protein structures share a high similarity with those of some Na+ channel scorpion toxins. LVP1 was not toxic to mice after intracerebro-ventricular injection. LVP1 stimulated lipolysis on freshly dissociated rat adipocytes in a dose-dependent manner with EC50 of â¼1+0.5 μg/ml. LVP1 subunits did not display any lipolytic activity. As previously described for venom, β adrenergic receptor (β AR) antagonists interfere with LVP1 activity. Furthermore, it is shown that LVP1 competes with [3H]-CGP 12177 (β1/β2 antagonist) for binding to adipocyte plasma membrane with an IC50 of about 10â7 M. These results demonstrate the existence of a new type of scorpion venom nontoxic peptides that are structurally related to Na+ channel toxins but can exert a distinct biological activity on adipocyte lipolysis through a β-type adrenoreceptor pathway.
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Physical Sciences and Engineering
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Analytical Chemistry
Authors
Nejla Soudani, Jouda Gharbi-Chihi, Najet Srairi-Abid, Claire Martin-El Yazidi, Richard Planells, Alain Margotat, Janine Torresani, Mohamed El Ayeb,