Abstract
Background Herein we report the discovery of a cystine-crosslinked peptide from Porifera along with high-quality spatial details accompanied by the description of its unique effect on neuronal calcium influx. Methods Asteropsin A (ASPA) was isolated from the marine sponge Asteropus sp., and its structure was independently determined using X-ray crystallography (0.87 Å) and solution NMR spectroscopy. Results An N-terminal pyroglutamate modification, uncommon cis proline conformations, and absence of basic residues helped distinguish ASPA from other cystine-crosslinked knot peptides. ASPA enhanced Ca2 + influx in murine cerebrocortical neuron cells following the addition of the Na+ channel activator veratridine but did not modify the oscillation frequency or amplitude of neuronal Ca2 + currents alone. Allosterism at neurotoxin site 2 was not observed, suggesting an alternative to the known Na+ channel interaction. Conclusions Together with a distinct biological activity, the origin of ASPA suggests a new subclass of cystine-rich knot peptides associated with Porifera. General significance The discovery of ASPA represents a distinctive addition to an emerging subclass of cystine-crosslinked knot peptides from Porifera.
Original language | English (US) |
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Pages (from-to) | 2591-2599 |
Number of pages | 9 |
Journal | Biochimica et Biophysica Acta - General Subjects |
Volume | 1830 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2013 |
All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology