CAJ | 학술논문

顺应蛋白质结构功能研究的发展对构象信息的需求,结合靶向分子动力学模拟和蛋白质网络方法建立了对β2肾上腺素受体激活信号传导相关的构象变化的解析方法,通过分子动力学模拟获取激活过程的构象集合,并进一步采用网络分析方法去识别构象变化过程中的关键残基及关键路径。结果表明,β2肾上腺素受体构象变化是各个区域之间信号传递的综合,跨膜螺旋的连接区域是信号传递的枢纽,螺旋两端包括胞内外Loop区域是信号传导的核心区域。关键路径分析发现,信号传递通路不止一条,都是从配体结合口袋残基Ser204附近开始,分别传递到NPxxY区域和ICL2区域,其中螺旋Ⅲ,吁,遇是信号传递的必经区域,这些研究成果为β2AR激活信号传导过程的阐明提供了重要的分子信息。
순응단백질결구공능연구적발전대구상신식적수구,결합파향분자동역학모의화단백질망락방법건립료대β2신상선소수체격활신호전도상관적구상변화적해석방법,통과분자동역학모의획취격활과정적구상집합,병진일보채용망락분석방법거식별구상변화과정중적관건잔기급관건로경。결과표명,β2신상선소수체구상변화시각개구역지간신호전체적종합,과막라선적련접구역시신호전체적추뉴,라선량단포괄포내외Loop구역시신호전도적핵심구역。관건로경분석발현,신호전체통로불지일조,도시종배체결합구대잔기Ser204부근개시,분별전체도NPxxY구역화ICL2구역,기중라선Ⅲ,우,우시신호전체적필경구역,저사연구성과위β2AR격활신호전도과정적천명제공료중요적분자신식。
To fill the urgent need of researches on the structure and function of proteins to obtain conformation information, we combined targeted molecular dynamics ( TMD) simulation with protein network methods to analyze conformation variations in the activation process of β2 adrenergic receptor. First, targeted MD was used to obtain the conformation resembles in the activation process, and then the protein network method was applied to identify the key residues and pathways in the activation process. The results indicate that the activa-tion process of β2 adrenergic receptor involves in the cooperation of all regions and the connector region of transmembrane helices is signaling hubs. In addition, the helix ends, including intracellular and extracellular loops, are the core areas. The pathway analysis reveals that there is more than one signaling pathway. All the pathways start from Ser204 of the ligand pocket and finally transmit to NPxxY or ICL2 region, which are depended on the different pathways. While the helix TMIII, TMV, TMVI are the important areas in all the pathways. The observations from the work provide valuable information at molecular level for unraveling the signal transduction mechanism associated with the activation process.