6 results on '"Wu, Yiran"'
Search Results
2. Structural basis of ligand recognition and self-activation of orphan GPR52
- Author
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Lin, Xi, Li, Mingyue, Wang, Niandong, Wu, Yiran, Luo, Zhipu, Guo, Shimeng, and Han, Gye-Won
- Subjects
Ligands (Biochemistry) -- Structure ,G proteins -- Physiological aspects ,Cell receptors -- Control ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
GPR52 is a class-A orphan G-protein-coupled receptor that is highly expressed in the brain and represents a promising therapeutic target for the treatment of Huntington's disease and several psychiatric disorders.sup.1,2. Pathological malfunction of GPR52 signalling occurs primarily through the heterotrimeric G.sub.s protein.sup.2, but it is unclear how GPR52 and G.sub.s couple for signal transduction and whether a native ligand or other activating input is required. Here we present the high-resolution structures of human GPR52 in three states: a ligand-free state, a G.sub.s-coupled self-activation state and a potential allosteric ligand-bound state. Together, our structures reveal that extracellular loop 2 occupies the orthosteric binding pocket and operates as a built-in agonist, conferring an intrinsically high level of basal activity to GPR52.sup.3. A fully active state is achieved when G.sub.s is coupled to GPR52 in the absence of an external agonist. The receptor also features a side pocket for ligand binding. These insights into the structure and function of GPR52 could improve our understanding of other self-activated GPCRs, enable the identification of endogenous and tool ligands, and guide drug discovery efforts that target GPR52. Structures of the orphan G-protein-coupled receptor GPR52 in ligand-free, G-protein-coupled and ligand-bound states reveal that extracellular loop 2 occupies the orthosteric binding pocket and functions as a built-in agonist to activate the receptor., Author(s): Xi Lin [sup.1] [sup.2] [sup.3] [sup.4] , Mingyue Li [sup.2] [sup.3] [sup.4] , Niandong Wang [sup.1] [sup.2] [sup.3] [sup.4] , Yiran Wu [sup.1] , Zhipu Luo [sup.5] , Shimeng [...]
- Published
- 2020
- Full Text
- View/download PDF
3. Crystal structure of the Frizzled 4 receptor in a ligand-free state
- Author
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Yang, Shifan, Wu, Yiran, Xu, Ting-Hai, de Waal, Parker W., He, Yuanzheng, Pu, Mengchen, and Chen, Yuxiang
- Subjects
Crystal structure -- Observations ,G proteins -- Physiological aspects -- Structure ,Molecular dynamics ,Proteins ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Frizzled receptors (FZDs) are class-F G-protein-coupled receptors (GPCRs) that function in Wnt signalling and are essential for developing and adult organisms.sup.1,2. As central mediators in this complex signalling pathway, FZDs serve as gatekeeping proteins both for drug intervention and for the development of probes in basic and in therapeutic research. Here we present an atomic-resolution structure of the human Frizzled 4 receptor (FZD4) transmembrane domain in the absence of a bound ligand. The structure reveals an unusual transmembrane architecture in which helix VI is short and tightly packed, and is distinct from all other GPCR structures reported so far. Within this unique transmembrane fold is an extremely narrow and highly hydrophilic pocket that is not amenable to the binding of traditional GPCR ligands. We show that such a pocket is conserved across all FZDs, which may explain the long-standing difficulties in the development of ligands for these receptors. Molecular dynamics simulations on the microsecond timescale and mutational analysis uncovered two coupled, dynamic kinks located at helix VII that are involved in FZD4 activation. The stability of the structure in its ligand-free form, an unfavourable pocket for ligand binding and the two unusual kinks on helix VII suggest that FZDs may have evolved a novel ligand-recognition and activation mechanism that is distinct from that of other GPCRs.The crystal structure of the Frizzled 4 receptor transmembrane domain is reported to a resolution of 2.4 Å in a ligand-free state., Author(s): Shifan Yang [sup.1] , Yiran Wu [sup.1] , Ting-Hai Xu [sup.2] , Parker W. de Waal [sup.2] , Yuanzheng He [sup.3] , Mengchen Pu [sup.1] , Yuxiang Chen [sup.1] [...]
- Published
- 2018
- Full Text
- View/download PDF
4. Crystal structures of agonist-bound human cannabinoid receptor CB1
- Author
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Hua, Tian, Vemuri, Kiran, Nikas, Spyros P., Laprairie, Robert B., Wu, Yiran, Qu, Lu, Pu, Mengchen, Korde, Anisha, Jiang, Shan, Ho, Jo-Hao, Han, Gye Won, Ding, Kang, Li, Xuanxuan, Liu, Haiguang, Hanson, Michael A., Zhao, Suwen, Bohn, Laura M., Makriyannis, Alexandros, Stevens, Raymond C., and Liu, Zhi-Jie
- Subjects
Cannabinoids -- Research ,Crystal structure -- Analysis ,Ligand binding (Biochemistry) -- Analysis ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Author(s): Tian Hua [1, 2, 3]; Kiran Vemuri [4]; Spyros P. Nikas [4]; Robert B. Laprairie [5]; Yiran Wu [1]; Lu Qu [1, 2, 3]; Mengchen Pu [1]; Anisha Korde [...]
- Published
- 2017
- Full Text
- View/download PDF
5. Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators
- Author
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Song, Gaojie, Yang, Dehua, Wang, Yuxia, de Graaf, Chris, Zhou, Qingtong, Jiang, Shanshan, Liu, Kaiwen, Cai, Xiaoqing, Dai, Antao, Lin, Guangyao, Liu, Dongsheng, Wu, Fan, Wu, Yiran, Zhao, Suwen, Ye, Li, Han, Gye Won, Lau, Jesper, Wu, Beili, Hanson, Michael A., Liu, Zhi-Jie, Wang, Ming-Wei, and Stevens, Raymond C.
- Subjects
Protein-protein interactions -- Health aspects ,Glucagon -- Health aspects ,Type 2 diabetes -- Physiological aspects ,Membrane proteins -- Health aspects ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Author(s): Gaojie Song [1]; Dehua Yang [2]; Yuxia Wang [1]; Chris de Graaf [3]; Qingtong Zhou [1]; Shanshan Jiang [4]; Kaiwen Liu [1, 5, 6]; Xiaoqing Cai [2]; Antao Dai [...]
- Published
- 2017
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- View/download PDF
6. Crystal structures of agonist-bound human cannabinoid receptor CB1.
- Author
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Hua, Tian, Vemuri, Kiran, Nikas, Spyros P., Laprairie, Robert B., Wu, Yiran, Qu, Lu, Pu, Mengchen, Korde, Anisha, Jiang, Shan, Ho, Jo-Hao, Han, Gye Won, Ding, Kang, Li, Xuanxuan, Liu, Haiguang, Hanson, Michael A., Zhao, Suwen, Bohn, Laura M., Makriyannis, Alexandros, Stevens, Raymond C., and Liu, Zhi-Jie
- Abstract
The cannabinoid receptor 1 (CB
1 ) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ9 -tetrahydrocannabinol (Δ9 -THC). Here we report two agonist-bound crystal structures of human CB1 in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841) at 2.80 Å and 2.95 Å resolution, respectively. The two CB1 -agonist complexes reveal important conformational changes in the overall structure, relative to the antagonist-bound state, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G-protein-binding region. In addition, a 'twin toggle switch' of Phe2003.36 and Trp3566.48 (superscripts denote Ballesteros-Weinstein numbering) is experimentally observed and appears to be essential for receptor activation. The structures reveal important insights into the activation mechanism of CB1 and provide a molecular basis for predicting the binding modes of Δ9 -THC, and endogenous and synthetic cannabinoids. The plasticity of the binding pocket of CB1 seems to be a common feature among certain class A G-protein-coupled receptors. These findings should inspire the design of chemically diverse ligands with distinct pharmacological properties. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
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