利用网络模型研究GPCR二聚体的结构和动力学性质（英文）
详细信息 查看官网全文
- 英文论文题名：Use Network Model to explore the structure and dynamic properties of GPCR dimers
- 论文作者：江源远 ; 张熙 ; 郭延芝 ; 李梦龙 ; 蒲雪梅
- 英文论文作者：Yuanyuan Jiang ; Xi Zhang ; Yanzhi Guo ; Menglong Li ; Xumei Pu ; Faculty of Chemistry ; Sichuan University
- 年：2016
- 作者机构：四川大学化学学院;
- 英文论文关键词：GPCR ; dimer ; Elastic Network Model ; Protein Structure Network
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十五分会：化学信息学与化学计量学
- 语种：英文
- 分类号：TQ460.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十五分会 ; 化学信息学与化学计量学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：163k
- 原文格式：D
- 会议级别：全国
摘要
GPCR plays a key role in signal transduction between intracellular and extracellular and has been important drug target.Recently,many experimental studies found that GPCRs can form the dimer or oligomer,which are another potential functional units besides their monomers.However,there have been absent of knowledge about structures,dynamics and functions of GPCR dimers.Thus,we,herein,we used the Elastic Network Model(ENM)and Protein Structure Network(PSN)to study the three GPCR dimers(viz.,CXCR4,κ-opioid R,β1AR)with different interfaces according to their basic topologic structures.The low-frequency modes from ENM indicate that the three GPCR monomers commonly present an antisymmetric rotation between extracelluar and intracellar motifs while their dimers exhibit an asymmetrical fluctuation between the two protomers,which should contribute to the negative cooperation between the two protomers and the asymmetric activation of GPCR dimers reported by experiments.PSN reveal that the dimerization can reduce informational flows characterized by the communication pathways between intracellular and extracellular,resulted from weakening restricts between TMs.The comparison between the monomer and protomer of the dimer shows that the TM1-TM2-H8 interface play more significant role in influencing the dynamics of the promoter with respect to TM5-TM6 one.Consequently,the most significant effect of the dimerization is observed forκ-opioid with TM1-TM2-H8 interface.B1AR also exhibits more difference between its monomer and dimer than CXCR4 due to larger contact areas in the interface ofβ1AR,although they have same TM4-TM5 interfaces.These observations from the work could provide valuable information for understanding the structure and function of GPCR dimers.
GPCR plays a key role in signal transduction between intracellular and extracellular and has been important drug target.Recently,many experimental studies found that GPCRs can form the dimer or oligomer,which are another potential functional units besides their monomers.However,there have been absent of knowledge about structures,dynamics and functions of GPCR dimers.Thus,we,herein,we used the Elastic Network Model(ENM) and Protein Structure Network(PSN) to study the three GPCR dimers(viz.,CXCR4,K-opioid R,β1AR) with different interfaces according to their basic topologic structures.The low-frequency modes from ENM indicate that the three GPCR monomers commonly present an antisymmetric rotation between extracelluar and intracellar motifs while their dimers exhibit an asymmetrical fluctuation between the two protomers,which should contribute to the negative cooperation between the two protomers and the asymmetric activation of GPCR dimers reported by experiments.PSN reveal that the dimerization can reduce informational flows characterized by the communication pathways between intracellular and extracellular,resulted from weakening restricts between TMs.The comparison between the monomer and protomer of the dimer shows that the TM1-TM2-H8 interface play more significant role in influencing the dynamics of the promoter with respect to TM5-TM6 one.Consequently,the most significant effect of the dimerization is observed for K-opioid with TM1-TM2-H8 interface.B1 AR also exhibits more difference between its monomer and dimer than CXCR4 due to larger contact areas in the interface of β1AR,although they have same TM4-TM5 interfaces.These observations from the work could provide valuable information for understanding the structure and function of GPCR dimers.
GPCR plays a key role in signal transduction between intracellular and extracellular and has been important drug target.Recently,many experimental studies found that GPCRs can form the dimer or oligomer,which are another potential functional units besides their monomers.However,there have been absent of knowledge about structures,dynamics and functions of GPCR dimers.Thus,we,herein,we used the Elastic Network Model(ENM) and Protein Structure Network(PSN) to study the three GPCR dimers(viz.,CXCR4,K-opioid R,β1AR) with different interfaces according to their basic topologic structures.The low-frequency modes from ENM indicate that the three GPCR monomers commonly present an antisymmetric rotation between extracelluar and intracellar motifs while their dimers exhibit an asymmetrical fluctuation between the two protomers,which should contribute to the negative cooperation between the two protomers and the asymmetric activation of GPCR dimers reported by experiments.PSN reveal that the dimerization can reduce informational flows characterized by the communication pathways between intracellular and extracellular,resulted from weakening restricts between TMs.The comparison between the monomer and protomer of the dimer shows that the TM1-TM2-H8 interface play more significant role in influencing the dynamics of the promoter with respect to TM5-TM6 one.Consequently,the most significant effect of the dimerization is observed for K-opioid with TM1-TM2-H8 interface.B1 AR also exhibits more difference between its monomer and dimer than CXCR4 due to larger contact areas in the interface of β1AR,although they have same TM4-TM5 interfaces.These observations from the work could provide valuable information for understanding the structure and function of GPCR dimers.
引文
[1]Marjorie,D.;Sophie,M.PNAS,2015,112:1601.
[2]Zeng,X.;Zhang,L.;Xiao,X.;Jiang,Y;Guo,Y;Li,M Pu,X,M*.Sci.Rep.2016,6:24065.
[3]Zhang,L,Y;Xiao,X,C;Yuan,Y;Guo,Y,Z;Li,M,L;Pu,X,M*.Sci.Rep.2015,5:9297
[4]Xiao,X.;Zeng,X.;Li,M.;Pu,X,M*.Phys.Chem.Chem.Phys.2015,17:2512.
[5]Hu,Y;Guo,Y*;Shi,Y;Li,M;Pu,X,M*.RSC Adv.,2015,5,42009
[2]Zeng,X.;Zhang,L.;Xiao,X.;Jiang,Y;Guo,Y;Li,M Pu,X,M*.Sci.Rep.2016,6:24065.
[3]Zhang,L,Y;Xiao,X,C;Yuan,Y;Guo,Y,Z;Li,M,L;Pu,X,M*.Sci.Rep.2015,5:9297
[4]Xiao,X.;Zeng,X.;Li,M.;Pu,X,M*.Phys.Chem.Chem.Phys.2015,17:2512.
[5]Hu,Y;Guo,Y*;Shi,Y;Li,M;Pu,X,M*.RSC Adv.,2015,5,42009