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
College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Biochim Biophys Acta. 2013 Mar;1830(3):2591-9. doi: 10.1016/j.bbagen.2012.11.015.
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.
Asteropsin A (ASPA) was isolated from the marine sponge Asteropus sp., and its structure was independently determined using X-ray crystallography (0.87 angstroms) and solution NMR spectroscopy.
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.
Together with a distinct biological activity, the origin of ASPA suggests a new subclass of cystine-rich knot peptides associated with Porifera.
The discovery of ASPA represents a distinctive addition to an emerging subclass of cystine-crosslinked knot peptides from Porifera.
在此我们报告从多孔动物中发现一种胱氨酸交联肽，同时呈现高质量的空间细节，并描述其对神经元钙内流的独特作用。
从海洋海绵星芒海绵属（Asteropus sp.）中分离出星芒视蛋白A（ASPA），并分别使用X射线晶体学（0.87埃）和溶液核磁共振光谱法确定其结构。
N端焦谷氨酸修饰、罕见的顺式脯氨酸构象以及缺乏碱性残基有助于将ASPA与其他胱氨酸交联结肽区分开来。在添加Na⁺通道激活剂藜芦定后，ASPA增强了小鼠大脑皮质神经元细胞中的Ca²⁺内流，但单独使用时并未改变神经元Ca²⁺电流的振荡频率或幅度。未观察到神经毒素位点2的变构现象，这表明存在一种不同于已知的与Na⁺通道相互作用的方式。
ASPA的起源连同其独特的生物活性表明与多孔动物相关的富含胱氨酸的结肽存在一个新的亚类。
ASPA的发现代表了来自多孔动物的胱氨酸交联结肽这一新兴亚类的一个独特补充。
