前往化源商城

Journal of Biological Chemistry 2015-07-17

Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.

Karolina Gwiazda, Gaetano Bonifacio, Sabrina Vullo, Stephan Kellenberger

文献索引:J. Biol. Chem. 290 , 17956-66, (2015)

全文:HTML全文

摘要

Acid-sensing ion channels (ASICs) are neuronal, voltage-independent Na(+) channels that are transiently activated by extracellular acidification. They are involved in pain sensation, the expression of fear, and in neurodegeneration after ischemic stroke. Our study investigates the role of extracellular subunit interactions in ASIC1a function. We identified two regions involved in critical intersubunit interactions. First, formation of an engineered disulfide bond between the palm and thumb domains leads to partial channel closure. Second, linking Glu-235 of a finger loop to either one of two different residues of the knuckle of a neighboring subunit opens the channel at physiological pH or disrupts its activity. This suggests that one finger-knuckle disulfide bond (E235C/K393C) sets the channel in an open state, whereas the other (E235C/Y389C) switches the channel to a non-conducting state. Voltage-clamp fluorometry experiments indicate that both the finger loop and the knuckle move away from the β-ball residue Trp-233 during acidification and subsequent desensitization. Together, these observations reveal that ASIC1a opening is accompanied by a distance increase between adjacent thumb and palm domains as well as a movement of Glu-235 relative to the knuckle helix. Our study identifies subunit interactions in the extracellular loop and shows that dynamic changes of these interactions are critical for normal ASIC function. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

相关化合物

结构式 名称/CAS号 全部文献
氢氧化钠 结构式 氢氧化钠
CAS:1310-73-2
氯化钠 结构式 氯化钠
CAS:7647-14-5
无水氯化钙 结构式 无水氯化钙
CAS:10043-52-4
3-乙基-2,4-戊烷二酮 结构式 3-乙基-2,4-戊烷二酮
CAS:1540-34-7
硫酸镁 结构式 硫酸镁
CAS:7487-88-9
4-羟乙基哌嗪乙磺酸 结构式 4-羟乙基哌嗪乙磺酸
CAS:7365-45-9
氯化钠-35cl 结构式 氯化钠-35cl
CAS:20510-55-8
氯化镁 结构式 氯化镁
CAS:7786-30-3
二水氯化钙 结构式 二水氯化钙
CAS:10035-04-8
3-马来酰亚胺基丙酸 结构式 3-马来酰亚胺基丙酸
CAS:7423-55-4