Agonism and antagonism in cyclic nucleotide-gated channels

环核苷酸门控通道中的激动和拮抗作用

• 批准号: 312124-2011
• 负责人: Young, Edgar
• 金额: $ 2.19万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526401
• 关键词: Agonism; antagonism; cyclic; nucleotide; gated

Cells control their life processes by producing natural chemical compounds (messengers) that bind to specific receptor proteins; in response, the receptors change their molecular structure in order to activate a particular biological function. Many physiological disorders, such as cancer and heart disease which afflict millions of Canadians, could be fought by artificial messengers (drugs) that either stimulate or suppress the ON- and OFF-switching of a specific receptor. My lab studies certain receptors called ion channels whose ON-conformation produces an electric current, so we can observe ON- and OFF-switching directly. We study a number of different ion channels, all of which respond to one type of messenger called cyclic nucleotide; this messenger is generated by the body under conditions of excitation, such as the "fight-or-flight" adrenaline rush, or during epileptic seizures in some parts of the brain. The molecules that form these ion channels all contain a specific sensing-domain which is the site for binding cyclic nucleotide. This sensing-domain obviously helps ON-switching after cyclic nucleotide is bound, but our lab has discovered that in different kinds of channels, the sensing-domain can do much more! For instance, in some channels, the sensing-domain will push the receptor OFF after being ON.

细胞通过产生与特定受体蛋白结合的天然化合物（信使）来控制其生命过程;作为响应，受体改变其分子结构以激活特定的生物功能。许多生理疾病，如折磨数百万加拿大人的癌症和心脏病，可以通过刺激或抑制特定受体的开启和关闭开关的人工信使（药物）来对抗。我的实验室研究了一种叫做离子通道的受体，它的开启构象会产生电流，所以我们可以直接观察到开启和关闭开关。我们研究了许多不同的离子通道，所有这些离子通道都对一种称为环核苷酸的信使做出反应;这种信使是由身体在兴奋条件下产生的，例如“战斗或逃跑”肾上腺素激增，或者在大脑某些部位的癫痫发作期间。形成这些离子通道的分子都含有一个特定的传感结构域，该结构域是结合环核苷酸的位点。这个传感结构域显然有助于环核苷酸结合后的开启开关，但我们的实验室发现，在不同类型的通道中，传感结构域可以做得更多！例如，在某些通道中，感知域会在开启后将受体推到关闭状态。