文献类型： 外文期刊

作者： Yadav, Gaya P. ¹ ; Zheng, Hui ² ; Yang, Qing ³ ; Douma, Lauren G. ⁴ ; Bloom, Linda B. ⁴ ; Jiang, Qiu-Xing ¹ ;

作者机构： 1.Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA

2.Univ Texas Southwestern Med Ctr Dallas, Dept Physiol, Dallas, TX USA

3.Henan Acad Agr Sci, Crop Designing Ctr, Zhengzhou, Henan, Peoples R China

4.Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA

期刊名称：LIFE SCIENCE ALLIANCE （ 影响因子：4.591； 五年影响因子：4.591 ）

ISSN：

年卷期： 2018 年 1 卷 5 期

页码：

收录情况： SCI

摘要： Regulated secretion is an intracellular pathway that is highly conserved from protists to humans. Granin family proteins were proposed to participate in the biogenesis, maturation and release of secretory granules in this pathway. However, the exact molecular mechanisms underlying the intracellular functions of the granin family proteins remain unclear. Here, we show that chromogranin B (CHGB), a secretory granule protein, inserts itself into membrane and forms a chloride-conducting channel. CHGB interacts strongly with phospholipid membranes through two amphipathic a helices. At a high local concentration, CHGB insertion in membrane causes significant bilayer remodeling, producing protein-coated nanoparticles and nanotubules. Fast kinetics and high cooperativity for anion efflux from CHGB vesicles suggest that CHGB tetramerizes to form a functional channel with a single-channel conductance of similar to 125 pS (150/150 mM Cl-). The CHGB channel is sensitive to an anion channel blocker and exhibits higher anion selectivity than the other six known families of Cl- channels. Our data suggest that the CHGB subfamily of granin proteins forms a new family of organelle chloride channels.