Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides.
Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides.
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DOI：
10.3390/ijms21218111
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发表时间：
2020-10-30
影响因子：
5.6
通讯作者：
Jiménez MA
中科院分区：
文献类型：
--
作者：
Morales P;Bruix M;Jiménez MA
大麻素CB 1受体的激活通过与不同的效应蛋白（G蛋白和β-抑制蛋白）偶联诱导不同的细胞信号传导级联，从而触发多种治疗效果。伴随配体结合的这种GPCR受体的胞内结构域的构象变化和重排决定了信号传导途径。G蛋白的GPCR结合界面已被广泛研究，而β-arrestin/GPCR复合物仍然知之甚少。为了获得这方面的知识，我们设计了模拟假定相互作用区域中涉及的基序的肽：β-抑制蛋白1指环和位于CB 1受体胞内侧的跨膜螺旋7-螺旋8（TMH 7-H8）肘。根据圆二色性和NMR数据，这些肽形成一个天然的，螺旋构象和相互作用，在水溶液中，在三氟乙醇的存在下，并使用两性离子洗涤剂胶束作为膜模拟物。这些结果增加了我们对β-arrestin和CB 1受体结合模式的理解，并验证了从结构上理解复杂蛋白质系统的最低限度方法。
Activation of the cannabinoid CB1 receptor induces different cellular signaling cascades through coupling to different effector proteins (G-proteins and β-arrestins), triggering numerous therapeutic effects. Conformational changes and rearrangements at the intracellular domain of this GPCR receptor that accompany ligand binding dictate the signaling pathways. The GPCR-binding interface for G proteins has been extensively studied, whereas β-arrestin/GPCR complexes are still poorly understood. To gain knowledge in this direction, we designed peptides that mimic the motifs involved in the putative interacting region: β-arrestin1 finger loop and the transmembrane helix 7-helix 8 (TMH7-H8) elbow located at the intracellular side of the CB1 receptor. According to circular dichroism and NMR data, these peptides form a native-like, helical conformation and interact with each other in aqueous solution, in the presence of trifluoroethanol, and using zwitterionic detergent micelles as membrane mimics. These results increase our understanding of the binding mode of β-arrestin and CB1 receptor and validate minimalist approaches to structurally comprehend complex protein systems.
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影响因子：
5.6
作者：
Ibsen, Mikkel Soes;Finlay, David B.;Grimsey, Natasha Lillia
通讯作者：
Grimsey, Natasha Lillia
影响因子：
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Kang Y;Zhou XE;Gao X;He Y;Liu W;Ishchenko A;Barty A;White TA;Yefanov O;Han GW;Xu Q;de Waal PW;Ke J;Tan MH;Zhang C;Moeller A;West GM;Pascal BD;Van Eps N;Caro LN;Vishnivetskiy SA;Lee RJ;Suino-Powell KM;Gu X;Pal K;Ma J;Zhi X;Boutet S;Williams GJ;Messerschmidt M;Gati C;Zatsepin NA;Wang D;James D;Basu S;Roy-Chowdhury S;Conrad CE;Coe J;Liu H;Lisova S;Kupitz C;Grotjohann I;Fromme R;Jiang Y;Tan M;Yang H;Li J;Wang M;Zheng Z;Li D;Howe N;Zhao Y;Standfuss J;Diederichs K;Dong Y;Potter CS;Carragher B;Caffrey M;Jiang H;Chapman HN;Spence JC;Fromme P;Weierstall U;Ernst OP;Katritch V;Gurevich VV;Griffin PR;Hubbell WL;Stevens RC;Cherezov V;Melcher K;Xu HE
通讯作者：
Xu HE
影响因子：
64.8
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Hua T;Vemuri K;Nikas SP;Laprairie RB;Wu Y;Qu L;Pu M;Korde A;Jiang S;Ho JH;Han GW;Ding K;Li X;Liu H;Hanson MA;Zhao S;Bohn LM;Makriyannis A;Stevens RC;Liu ZJ
通讯作者：
Liu ZJ
影响因子：
16.6
作者：
Flores-Otero J;Ahn KH;Delgado-Peraza F;Mackie K;Kendall DA;Yudowski GA
通讯作者：
Yudowski GA
影响因子：
7.3
作者：
Finlay, David B.;Cawston, Erin E.;Glass, Michelle
通讯作者：
Glass, Michelle