β2肾上腺素受体(β2adrenergic receptor,β2AR)是G蛋白耦联受体(G protein coupled receptors,GPCRs)超家族中的一员,也是研究治疗哮喘的关键药物受体靶标.采用进化踪迹(evolutionary trace,ET)方法分析肾上腺素受体家族跨膜区片段序...β2肾上腺素受体(β2adrenergic receptor,β2AR)是G蛋白耦联受体(G protein coupled receptors,GPCRs)超家族中的一员,也是研究治疗哮喘的关键药物受体靶标.采用进化踪迹(evolutionary trace,ET)方法分析肾上腺素受体家族跨膜区片段序列,识别出了44个保守的残基,然后将β2肾上腺素受体以及受体D130N活性突变体、D79N失活突变体进行分子动力学模拟,试图找出与受体不同功能状态相关的结构动力学特征.发现受体DRY motif中的D130远离R131而转向K149残基这一结构特征与受体活性高度关联,此外,从残基相互作用的变化推断出了受体helix 2,4 and 6伴随着受体活化而发生的运动.这些研究结果对进一步探索β2肾上腺素受体突变体的激活机制以及所诱发疾病的分子机理提供了依据.展开更多
The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavi-rus (CoV). Several sequences of the complete genome of SARS-CoV have been determined. The subcellu-lar localization (SubLocat...The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavi-rus (CoV). Several sequences of the complete genome of SARS-CoV have been determined. The subcellu-lar localization (SubLocation) of annotated open-reading frames of the SARS-CoV genome was predicted using a support vector machine. Several gene products were predicted to locate in the Golgi body and cell nucleus. The SubLocation information was combined with predicted transmembrane information to develop a model of the viral life cycle. The results show that this information can be used to predict the functions of genes and even the virus pathogenesis. In addition, the entire SARS viral genome sequences currently available in GenBank were compared to identify the sequence variations among different isolates. Some variations in the Hong Kong strains may be related to the special clinical manifestations and provide clues for understanding the relationship between gene functions and evolution. These variations reflect the evolu-tion of the SARS virus in human populations and may help development of a vaccine.展开更多
文摘β2肾上腺素受体(β2adrenergic receptor,β2AR)是G蛋白耦联受体(G protein coupled receptors,GPCRs)超家族中的一员,也是研究治疗哮喘的关键药物受体靶标.采用进化踪迹(evolutionary trace,ET)方法分析肾上腺素受体家族跨膜区片段序列,识别出了44个保守的残基,然后将β2肾上腺素受体以及受体D130N活性突变体、D79N失活突变体进行分子动力学模拟,试图找出与受体不同功能状态相关的结构动力学特征.发现受体DRY motif中的D130远离R131而转向K149残基这一结构特征与受体活性高度关联,此外,从残基相互作用的变化推断出了受体helix 2,4 and 6伴随着受体活化而发生的运动.这些研究结果对进一步探索β2肾上腺素受体突变体的激活机制以及所诱发疾病的分子机理提供了依据.
基金the National High-Tech Research and Devel-opment (863) Program of China (No. 2002AA234041) the National Natural Science Foundation of China (No. 90303017)and the National Key Basic Research and Development (973) Program of China (No. 2003CB715903)
文摘The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavi-rus (CoV). Several sequences of the complete genome of SARS-CoV have been determined. The subcellu-lar localization (SubLocation) of annotated open-reading frames of the SARS-CoV genome was predicted using a support vector machine. Several gene products were predicted to locate in the Golgi body and cell nucleus. The SubLocation information was combined with predicted transmembrane information to develop a model of the viral life cycle. The results show that this information can be used to predict the functions of genes and even the virus pathogenesis. In addition, the entire SARS viral genome sequences currently available in GenBank were compared to identify the sequence variations among different isolates. Some variations in the Hong Kong strains may be related to the special clinical manifestations and provide clues for understanding the relationship between gene functions and evolution. These variations reflect the evolu-tion of the SARS virus in human populations and may help development of a vaccine.
