The first gamma-carboxyglutamic acid-containing contryphan. A selective L-type calcium ion channel blocker isolated from the venom of Conus marmoreus
| العنوان: | The first gamma-carboxyglutamic acid-containing contryphan. A selective L-type calcium ion channel blocker isolated from the venom of Conus marmoreus |
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| المؤلفون: | Hansson, K, Ma, X, Eliasson, L, Czerwiec, E, Furie, B, Rorsman, P, Stenflo, J |
| المصدر: | The Journal of biological chemistry. 279(31) |
| سنة النشر: | 2004 |
| الوصف: | Contryphans constitute a group of conopeptides that are known to contain an unusual density of post-translational modifications including tryptophan bromination, amidation of the C-terminal residue, leucine, and tryptophan isomerization, and proline hydroxylation. Here we report the identification and characterization of a new member of this family, glacontryphan-M from the venom of Conus marmoreus. This is the first known example of a contryphan peptide carrying glutamyl residues that have been post-translationally carboxylated to gamma-carboxyglutamyl (Gla) residues. The amino acid sequence of glacontryphan-M was determined using automated Edman degradation and electrospray ionization mass spectrometry. The amino acid sequence of the peptide is: Asn-Gla-Ser-Gla-Cys-Pro-D-Trp-His-Pro-Trp-Cys. As with most other contryphans, glacontryphan-M is amidated at the C terminus and maintains the five-residue intercysteine loop. The occurrence of a D-tryptophan residue was confirmed by chemical synthesis and HPLC elution profiles. Using fluorescence spectroscopy we demonstrated that the Gla-containing peptide binds calcium with a K(D) of 0.63 mM. Cloning of the full-length cDNA encoding glacontryphan-M revealed that the primary translation product carries an N-terminal signal/propeptide sequence that is homologous to earlier reported contryphan signal/propeptide sequences up to 10 amino acids preceding the toxin region. Electrophysiological experiments, carried out on mouse pancreatic B-cells, showed that glacontryphan-M blocks L-type voltage-gated calcium ion channel activity in a calcium-dependent manner. Glacontryphan-M is the first contryphan reported to modulate the activity of L-type calcium ion channels. |
| اللغة: | English |
| تدمد: | 1083-351X 0021-9258 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::8a7ee510cd2b6ba7eafc0fea8d9b8bf1 http://ora.ox.ac.uk/objects/uuid:855f67bb-73e2-4745-8b4e-9d138b289800 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.dedup.wf.001..8a7ee510cd2b6ba7eafc0fea8d9b8bf1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1083351X 00219258 |
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