Asteropsin A: An unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2 + influx

Huayue Li, John J. Bowling, Frank R. Fronczek, Jongki Hong, Sairam V. Jabba, Thomas F. Murray, Nam Chul Ha, Mark T. Hamann, Jee H. Jung

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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 languageEnglish (US)
Pages (from-to)2591-2599
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1830
Issue number3
DOIs
StatePublished - Mar 1 2013

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Li, H., Bowling, J. J., Fronczek, F. R., Hong, J., Jabba, S. V., Murray, T. F., Ha, N. C., Hamann, M. T., & Jung, J. H. (2013). Asteropsin A: An unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2 + influx. Biochimica et Biophysica Acta - General Subjects, 1830(3), 2591-2599. https://doi.org/10.1016/j.bbagen.2012.11.015