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 |
|---|---|
| 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 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Biophysics
- Molecular Biology
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Asteropsin A : An unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2 + influx. / Li, Huayue; Bowling, John J.; Fronczek, Frank R.; Hong, Jongki; Jabba, Sairam V.; Murray, Thomas F.; Ha, Nam Chul; Hamann, Mark T.; Jung, Jee H.
In: Biochimica et Biophysica Acta - General Subjects, Vol. 1830, No. 3, 03.2013, p. 2591-2599.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Asteropsin A
T2 - An unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2 + influx
AU - Li, Huayue
AU - Bowling, John J.
AU - Fronczek, Frank R.
AU - Hong, Jongki
AU - Jabba, Sairam V.
AU - Murray, Thomas F.
AU - Ha, Nam Chul
AU - Hamann, Mark T.
AU - Jung, Jee H.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84872818821&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2012.11.015
DO - 10.1016/j.bbagen.2012.11.015
M3 - Article
VL - 1830
SP - 2591
EP - 2599
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
SN - 0006-3002
IS - 3
ER -