Dominant Negative G Proteins Enhance Formation and Purification of Agonist-GPCR-G Protein Complexes for Structure Determination
- Yi-Lynn LiangYi-Lynn LiangDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Yi-Lynn Liang
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- Peishen ZhaoPeishen ZhaoDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Peishen Zhao
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- Christopher Draper-JoyceChristopher Draper-JoyceDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Christopher Draper-Joyce
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- Jo-Anne BaltosJo-Anne BaltosDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Jo-Anne Baltos
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- Alisa GlukhovaAlisa GlukhovaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Alisa Glukhova
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- Tin T. TruongTin T. TruongDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Tin T. Truong
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- Lauren T. MayLauren T. MayDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Lauren T. May
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- Arthur ChristopoulosArthur ChristopoulosDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Arthur Christopoulos
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- Denise Wootten*Denise Wootten*E-mail: [email protected]Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaSchool of Pharmacy, Fudan University, Shanghai 201203, ChinaMore by Denise Wootten
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- Patrick M. Sexton*Patrick M. Sexton*E-mail: [email protected]Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaSchool of Pharmacy, Fudan University, Shanghai 201203, ChinaMore by Patrick M. Sexton
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- Sebastian G. B. Furness*Sebastian G. B. Furness*E-mail: [email protected]Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, AustraliaMore by Sebastian G. B. Furness
Abstract

Advances in structural biology have yielded exponential growth in G protein-coupled receptor (GPCR) structure solution. Nonetheless, the instability of fully active GPCR complexes with cognate heterotrimeric G proteins has made them elusive. Existing structures have been limited to nanobody-stabilized GPCR:Gs complexes. Here we present methods for enhanced GPCR:G protein complex stabilization via engineering G proteins with reduced nucleotide affinity, limiting Gα:Gβγ dissociation. We illustrate the application of dominant negative G proteins of Gαs and Gαi2 to the purification of stable complexes where this was not possible with wild-type G protein. Active state complexes of adenosine:A1 receptor:Gαi2βγ and calcitonin gene-related peptide (CGRP):CLR:RAMP1:Gαsβγ:Nb35 were purified to homogeneity and were stable in negative stain electron microscopy. These were suitable for structure determination by cryo-electron microscopy at 3.6 and 3.3 Å resolution, respectively. The dominant negative Gα-proteins are thus high value tools for structure determination of agonist:GPCR:G protein complexes that are critical for informed translational drug discovery.
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- Jie Zhao, Hong Fu, Jingjing Yu, Weiqi Hong, Xiaowen Tian, Jieyu Qi, Suyue Sun, Chang Zhao, Chao Wu, Zheng Xu, Lin Cheng, Renjie Chai, Wei Yan, Xiawei Wei, Zhenhua Shao. Prospect of acromegaly therapy: molecular mechanism of clinical drugs octreotide and paltusotine. Nature Communications 2023, 14 (1) https://doi.org/10.1038/s41467-023-36673-z
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- Dongqi Zhang, Yongfeng Liu, Saheem A Zaidi, Lingyi Xu, Yuting Zhan, Anqi Chen, Jiangtao Guo, Xi‐Ping Huang, Bryan L Roth, Vsevolod Katritch, Vadim Cherezov, Haitao Zhang. Structural insights into angiotensin receptor signaling modulation by balanced and biased agonists. The EMBO Journal 2023, 42 (11) https://doi.org/10.15252/embj.2022112940
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- Peiyu Xu, Sijie Huang, Brian E. Krumm, Youwen Zhuang, Chunyou Mao, Yumu Zhang, Yue Wang, Xi-Ping Huang, Yong-Feng Liu, Xinheng He, Huadong Li, Wanchao Yin, Yi Jiang, Yan Zhang, Bryan L. Roth, H. Eric Xu. Structural genomics of the human dopamine receptor system. Cell Research 2023, 16 https://doi.org/10.1038/s41422-023-00808-0
- Jianming Han, Jingying Zhang, Antonina L. Nazarova, Sarah M. Bernhard, Brian E. Krumm, Lei Zhao, Jordy Homing Lam, Vipin A. Rangari, Susruta Majumdar, David E. Nichols, Vsevolod Katritch, Peng Yuan, Jonathan F. Fay, Tao Che. Ligand and G-protein selectivity in the κ-opioid receptor. Nature 2023, 617 (7960) , 417-425. https://doi.org/10.1038/s41586-023-06030-7
- Brian P Cary, Xin Zhang, Jianjun Cao, Rachel M Johnson, Sarah J Piper, Elliot J Gerrard, Denise Wootten, Patrick M Sexton. New Insights into the Structure and Function of Class B1 GPCRs. Endocrine Reviews 2023, 44 (3) , 492-517. https://doi.org/10.1210/endrev/bnac033
- Yuying Feng, Chang Zhao, Yue Deng, Heli Wang, Liang Ma, Sicen Liu, Xiaowen Tian, Bo Wang, Yan Bin, Peipei Chen, Wei Yan, Ping Fu, Zhenhua Shao. Mechanism of activation and biased signaling in complement receptor C5aR1. Cell Research 2023, 33 (4) , 312-324. https://doi.org/10.1038/s41422-023-00779-2
- Yue Wang, Youwen Zhuang, Jeffrey F. DiBerto, X. Edward Zhou, Gavin P. Schmitz, Qingning Yuan, Manish K. Jain, Weiyi Liu, Karsten Melcher, Yi Jiang, Bryan L. Roth, H. Eric Xu. Structures of the entire human opioid receptor family. Cell 2023, 186 (2) , 413-427.e17. https://doi.org/10.1016/j.cell.2022.12.026
- Manish K. Yadav, Vinay Singh, Sayantan Saha, Arun K. Shukla. A streamlined protocol for expression and purification of wild-type β-arrestins. 2023, 465-475. https://doi.org/10.1016/bs.mie.2022.12.006
- Xiuwen Zhai, Chunyou Mao, Qingya Shen, Shaokun Zang, Dan-Dan Shen, Huibing Zhang, Zhaohong Chen, Gang Wang, Changming Zhang, Yan Zhang, Zhihong Liu. Molecular insights into the distinct signaling duration for the peptide-induced PTH1R activation. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-34009-x
- Sarah J. Piper, Giuseppe Deganutti, Jessica Lu, Peishen Zhao, Yi-Lynn Liang, Yao Lu, Madeleine M. Fletcher, Mohammed Akhter Hossain, Arthur Christopoulos, Christopher A. Reynolds, Radostin Danev, Patrick M. Sexton, Denise Wootten. Understanding VPAC receptor family peptide binding and selectivity. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-34629-3
- Giuseppe Deganutti, Yi-Lynn Liang, Xin Zhang, Maryam Khoshouei, Lachlan Clydesdale, Matthew J. Belousoff, Hari Venugopal, Tin T. Truong, Alisa Glukhova, Andrew N. Keller, Karen J. Gregory, Katie Leach, Arthur Christopoulos, Radostin Danev, Christopher A. Reynolds, Peishen Zhao, Patrick M. Sexton, Denise Wootten. Dynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-021-27760-0
- Fenghui Zhao, Qingtong Zhou, Zhaotong Cong, Kaini Hang, Xinyu Zou, Chao Zhang, Yan Chen, Antao Dai, Anyi Liang, Qianqian Ming, Mu Wang, Li-Nan Chen, Peiyu Xu, Rulve Chang, Wenbo Feng, Tian Xia, Yan Zhang, Beili Wu, Dehua Yang, Lihua Zhao, H. Eric Xu, Ming-Wei Wang. Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-28683-0
- Shota Suzuki, Momoko Iida, Yoko Hiroaki, Kotaro Tanaka, Akihiro Kawamoto, Takayuki Kato, Atsunori Oshima. Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM. Communications Biology 2022, 5 (1) https://doi.org/10.1038/s42003-022-03668-3
- Wenli Zhao, Wenru Zhang, Mu Wang, Minmin Lu, Shutian Chen, Tingting Tang, Gisela Schnapp, Holger Wagner, Albert Brennauer, Cuiying Yi, Xiaojing Chu, Shuo Han, Beili Wu, Qiang Zhao. Ligand recognition and activation of neuromedin U receptor 2. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-34814-4
- Jia Duan, Peiyu Xu, Xiaodong Luan, Yujie Ji, Xinheng He, Ning Song, Qingning Yuan, Ye Jin, Xi Cheng, Hualiang Jiang, Jie Zheng, Shuyang Zhang, Yi Jiang, H. Eric Xu. Hormone- and antibody-mediated activation of the thyrotropin receptor. Nature 2022, 609 (7928) , 854-859. https://doi.org/10.1038/s41586-022-05173-3
- Peiyu Xu, Sijie Huang, Shimeng Guo, Ying Yun, Xi Cheng, Xinheng He, Pengjun Cai, Yuan Lan, Hu Zhou, Hualiang Jiang, Yi Jiang, Xin Xie, H. Eric Xu. Structural identification of lysophosphatidylcholines as activating ligands for orphan receptor GPR119. Nature Structural & Molecular Biology 2022, 29 (9) , 863-870. https://doi.org/10.1038/s41594-022-00816-5
- Sijie Huang, Peiyu Xu, Dan-Dan Shen, Icaro A. Simon, Chunyou Mao, Yangxia Tan, Huibing Zhang, Kasper Harpsøe, Huadong Li, Yumu Zhang, Chongzhao You, Xuekui Yu, Yi Jiang, Yan Zhang, David E. Gloriam, H. Eric Xu. GPCRs steer Gi and Gs selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors. Molecular Cell 2022, 82 (14) , 2681-2695.e6. https://doi.org/10.1016/j.molcel.2022.05.031
- Zhaotong Cong, Yi-Lynn Liang, Qingtong Zhou, Sanaz Darbalaei, Fenghui Zhao, Wenbo Feng, Lihua Zhao, H. Eric Xu, Dehua Yang, Ming-Wei Wang. Structural perspective of class B1 GPCR signaling. Trends in Pharmacological Sciences 2022, 43 (4) , 321-334. https://doi.org/10.1016/j.tips.2022.01.002
- Jianjun Cao, Matthew J. Belousoff, Yi-Lynn Liang, Rachel M. Johnson, Tracy M. Josephs, Madeleine M. Fletcher, Arthur Christopoulos, Debbie L. Hay, Radostin Danev, Denise Wootten, Patrick M. Sexton. A structural basis for amylin receptor phenotype. Science 2022, 375 (6587) https://doi.org/10.1126/science.abm9609
- Brian P. Cary, Giuseppe Deganutti, Peishen Zhao, Tin T. Truong, Sarah J. Piper, Xinyu Liu, Matthew J. Belousoff, Radostin Danev, Patrick M. Sexton, Denise Wootten, Samuel H. Gellman. Structural and functional diversity among agonist-bound states of the GLP-1 receptor. Nature Chemical Biology 2022, 18 (3) , 256-263. https://doi.org/10.1038/s41589-021-00945-w
- Joshua A. Lees, Joao M. Dias, Seungil Han. Applications of Cryo-EM in small molecule and biologics drug design. Biochemical Society Transactions 2021, 49 (6) , 2627-2638. https://doi.org/10.1042/BST20210444
- Fan Yang, Lulu Guo, Yu Li, Guopeng Wang, Jia Wang, Chao Zhang, Guo-Xing Fang, Xu Chen, Lei Liu, Xu Yan, Qun Liu, Changxiu Qu, Yunfei Xu, Peng Xiao, Zhongliang Zhu, Zijian Li, Jiuyao Zhou, Xiao Yu, Ning Gao, Jin-Peng Sun. Structure, function and pharmacology of human itch receptor complexes. Nature 2021, 600 (7887) , 164-169. https://doi.org/10.1038/s41586-021-04077-y
- Zhaotong Cong, Li-Nan Chen, Honglei Ma, Qingtong Zhou, Xinyu Zou, Chenyu Ye, Antao Dai, Qing Liu, Wei Huang, Xianqiang Sun, Xi Wang, Peiyu Xu, Lihua Zhao, Tian Xia, Wenge Zhong, Dehua Yang, H. Eric Xu, Yan Zhang, Ming-Wei Wang. Molecular insights into ago-allosteric modulation of the human glucagon-like peptide-1 receptor. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-24058-z
- Huibing Zhang, Li-Nan Chen, Dehua Yang, Chunyou Mao, Qingya Shen, Wenbo Feng, Dan-Dan Shen, Antao Dai, Shanshan Xie, Yan Zhou, Jiao Qin, Jin-Peng Sun, Daniel H. Scharf, Tingjun Hou, Tianhua Zhou, Ming-Wei Wang, Yan Zhang. Structural insights into ligand recognition and activation of the melanocortin-4 receptor. Cell Research 2021, 31 (11) , 1163-1175. https://doi.org/10.1038/s41422-021-00552-3
- Jia Duan, Peiyu Xu, Xi Cheng, Chunyou Mao, Tristan Croll, Xinheng He, Jingjing Shi, Xiaodong Luan, Wanchao Yin, Erli You, Qiufeng Liu, Shuyang Zhang, Hualiang Jiang, Yan Zhang, Yi Jiang, H. Eric Xu. Structures of full-length glycoprotein hormone receptor signalling complexes. Nature 2021, 598 (7882) , 688-692. https://doi.org/10.1038/s41586-021-03924-2
- Zhaotong Cong, Fulai Zhou, Chao Zhang, Xinyu Zou, Huibing Zhang, Yuzhe Wang, Qingtong Zhou, Xiaoqing Cai, Qiaofeng Liu, Jie Li, Lijun Shao, Chunyou Mao, Xi Wang, Jihong Wu, Tian Xia, Li-Hua Zhao, Hualiang Jiang, Yan Zhang, H. Eric Xu, Xi Cheng, Dehua Yang, Ming-Wei Wang. Constitutive signal bias mediated by the human GHRHR splice variant 1. Proceedings of the National Academy of Sciences 2021, 118 (40) https://doi.org/10.1073/pnas.2106606118
- Christopher J. Draper-Joyce, Rebecca Bhola, Jinan Wang, Apurba Bhattarai, Anh T. N. Nguyen, India Cowie-Kent, Kelly O’Sullivan, Ling Yeong Chia, Hariprasad Venugopal, Celine Valant, David M. Thal, Denise Wootten, Nicolas Panel, Jens Carlsson, Macdonald J. Christie, Paul J. White, Peter Scammells, Lauren T. May, Patrick M. Sexton, Radostin Danev, Yinglong Miao, Alisa Glukhova, Wendy L. Imlach, Arthur Christopoulos. Positive allosteric mechanisms of adenosine A1 receptor-mediated analgesia. Nature 2021, 597 (7877) , 571-576. https://doi.org/10.1038/s41586-021-03897-2
- Xin Zhang, Rachel M. Johnson, Ieva Drulyte, Lingbo Yu, Abhay Kotecha, Radostin Danev, Denise Wootten, Patrick M. Sexton, Matthew J. Belousoff. Evolving cryo-EM structural approaches for GPCR drug discovery. Structure 2021, 29 (9) , 963-974.e6. https://doi.org/10.1016/j.str.2021.04.008
- Xi Wang, Xi Cheng, Lihua Zhao, Yuzhe Wang, Chenyu Ye, Xinyu Zou, Antao Dai, Zhaotong Cong, Jian Chen, Qingtong Zhou, Tian Xia, Hualiang Jiang, H. Eric Xu, Dehua Yang, Ming-Wei Wang. Molecular insights into differentiated ligand recognition of the human parathyroid hormone receptor 2. Proceedings of the National Academy of Sciences 2021, 118 (32) https://doi.org/10.1073/pnas.2101279118
- Fenghui Zhao, Chao Zhang, Qingtong Zhou, Kaini Hang, Xinyu Zou, Yan Chen, Fan Wu, Qidi Rao, Antao Dai, Wanchao Yin, Dan-Dan Shen, Yan Zhang, Tian Xia, Raymond C Stevens, Eric Xu, Dehua Yang, Lihua Zhao, Ming-Wei Wang. Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor. eLife 2021, 10 https://doi.org/10.7554/eLife.68719
- Xin Zhang, Matthew J. Belousoff, Yi-Lynn Liang, Radostin Danev, Patrick M. Sexton, Denise Wootten. Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes. Cell Reports 2021, 36 (2) , 109374. https://doi.org/10.1016/j.celrep.2021.109374
- Jesse I. Mobbs, Matthew J. Belousoff, Kaleeckal G. Harikumar, Sarah J. Piper, Xiaomeng Xu, Sebastian G. B. Furness, Hari Venugopal, Arthur Christopoulos, Radostin Danev, Denise Wootten, David M. Thal, Laurence J. Miller, Patrick M. Sexton, . Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity. PLOS Biology 2021, 19 (6) , e3001295. https://doi.org/10.1371/journal.pbio.3001295
- Peiyu Xu, Sijie Huang, Huibing Zhang, Chunyou Mao, X. Edward Zhou, Xi Cheng, Icaro A. Simon, Dan-Dan Shen, Hsin-Yung Yen, Carol V. Robinson, Kasper Harpsøe, Bo Svensson, Jia Guo, Hualiang Jiang, David E. Gloriam, Karsten Melcher, Yi Jiang, Yan Zhang, H. Eric Xu. Structural insights into the lipid and ligand regulation of serotonin receptors. Nature 2021, 592 (7854) , 469-473. https://doi.org/10.1038/s41586-021-03376-8
- Tracy M. Josephs, Matthew J. Belousoff, Yi-Lynn Liang, Sarah J. Piper, Jianjun Cao, Daniel J. Garama, Katie Leach, Karen J. Gregory, Arthur Christopoulos, Debbie L. Hay, Radostin Danev, Denise Wootten, Patrick M. Sexton. Structure and dynamics of the CGRP receptor in apo and peptide-bound forms. Science 2021, 372 (6538) https://doi.org/10.1126/science.abf7258
- Yann Waltenspühl, Janosch Ehrenmann, Christoph Klenk, Andreas Plückthun. Engineering of Challenging G Protein-Coupled Receptors for Structure Determination and Biophysical Studies. Molecules 2021, 26 (5) , 1465. https://doi.org/10.3390/molecules26051465
- Peiyu Xu, Sijie Huang, Chunyou Mao, Brian E. Krumm, X. Edward Zhou, Yangxia Tan, Xi-Ping Huang, Yongfeng Liu, Dan-Dan Shen, Yi Jiang, Xuekui Yu, Hualiang Jiang, Karsten Melcher, Bryan L. Roth, Xi Cheng, Yan Zhang, H. Eric Xu. Structures of the human dopamine D3 receptor-Gi complexes. Molecular Cell 2021, 81 (6) , 1147-1159.e4. https://doi.org/10.1016/j.molcel.2021.01.003
- Youwen Zhuang, Peiyu Xu, Chunyou Mao, Lei Wang, Brian Krumm, X. Edward Zhou, Sijie Huang, Heng Liu, Xi Cheng, Xi-Ping Huang, Dan-Dan Shen, Tinghai Xu, Yong-Feng Liu, Yue Wang, Jia Guo, Yi Jiang, Hualiang Jiang, Karsten Melcher, Bryan L. Roth, Yan Zhang, Cheng Zhang, H. Eric Xu. Structural insights into the human D1 and D2 dopamine receptor signaling complexes. Cell 2021, 184 (4) , 931-942.e18. https://doi.org/10.1016/j.cell.2021.01.027
- Christoph Wigge, Aleksandar Stefanovic, Mazdak Radjainia. The rapidly evolving role of cryo-EM in drug design. Drug Discovery Today: Technologies 2020, 38 , 91-102. https://doi.org/10.1016/j.ddtec.2020.12.003
- Maoqing Dong, Giuseppe Deganutti, Sarah J. Piper, Yi-Lynn Liang, Maryam Khoshouei, Matthew J. Belousoff, Kaleeckal G. Harikumar, Christopher A. Reynolds, Alisa Glukhova, Sebastian G. B. Furness, Arthur Christopoulos, Radostin Danev, Denise Wootten, Patrick M. Sexton, Laurence J. Miller. Structure and dynamics of the active Gs-coupled human secretin receptor. Nature Communications 2020, 11 (1) https://doi.org/10.1038/s41467-020-17791-4
- Fulai Zhou, Huibing Zhang, Zhaotong Cong, Li-Hua Zhao, Qingtong Zhou, Chunyou Mao, Xi Cheng, Dan-Dan Shen, Xiaoqing Cai, Cheng Ma, Yuzhe Wang, Antao Dai, Yan Zhou, Wen Sun, Fenghui Zhao, Suwen Zhao, Hualiang Jiang, Yi Jiang, Dehua Yang, H. Eric Xu, Yan Zhang, Ming-Wei Wang. Structural basis for activation of the growth hormone-releasing hormone receptor. Nature Communications 2020, 11 (1) https://doi.org/10.1038/s41467-020-18945-0
- Xin Zhang, Matthew J. Belousoff, Peishen Zhao, Albert J. Kooistra, Tin T. Truong, Sheng Yu Ang, Christina Rye Underwood, Thomas Egebjerg, Petr Šenel, Gregory D. Stewart, Yi-Lynn Liang, Alisa Glukhova, Hari Venugopal, Arthur Christopoulos, Sebastian G.B. Furness, Laurence J. Miller, Steffen Reedtz-Runge, Christopher J. Langmead, David E. Gloriam, Radostin Danev, Patrick M. Sexton, Denise Wootten. Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists. Molecular Cell 2020, 80 (3) , 485-500.e7. https://doi.org/10.1016/j.molcel.2020.09.020
- Rulue Chang, Xin Zhang, Anna Qiao, Antao Dai, Matthew J. Belousoff, Qiuxiang Tan, Lijun Shao, Li Zhong, Guangyao Lin, Yi-Lynn Liang, Limin Ma, Shuo Han, Dehua Yang, Radostin Danev, Ming-Wei Wang, Denise Wootten, Beili Wu, Patrick M. Sexton. Cryo-electron microscopy structure of the glucagon receptor with a dual-agonist peptide. Journal of Biological Chemistry 2020, 295 (28) , 9313-9325. https://doi.org/10.1074/jbc.RA120.013793
- James C. Errey, Cédric Fiez-Vandal. Production of membrane proteins in industry: The example of GPCRs. Protein Expression and Purification 2020, 169 , 105569. https://doi.org/10.1016/j.pep.2020.105569
- Yi-Lynn Liang, Matthew J. Belousoff, Peishen Zhao, Cassandra Koole, Madeleine M. Fletcher, Tin T. Truong, Villy Julita, George Christopoulos, H. Eric Xu, Yan Zhang, Maryam Khoshouei, Arthur Christopoulos, Radostin Danev, Patrick M. Sexton, Denise Wootten. Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation. Molecular Cell 2020, 77 (3) , 656-668.e5. https://doi.org/10.1016/j.molcel.2020.01.012
- Changrui Xing, Youwen Zhuang, Ting-Hai Xu, Zhiwei Feng, X. Edward Zhou, Maozi Chen, Lei Wang, Xing Meng, Ying Xue, Junmei Wang, Heng Liu, Terence Francis McGuire, Gongpu Zhao, Karsten Melcher, Cheng Zhang, H. Eric Xu, Xiang-Qun Xie. Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. Cell 2020, 180 (4) , 645-654.e13. https://doi.org/10.1016/j.cell.2020.01.007
- Przemyslaw Dutka, Somnath Mukherjee, Xiang Gao, Yanyong Kang, Parker W. de Waal, Lei Wang, Youwen Zhuang, Karsten Melcher, Cheng Zhang, H. Eric Xu, Anthony A. Kossiakoff. Development of “Plug and Play” Fiducial Marks for Structural Studies of GPCR Signaling Complexes by Single-Particle Cryo-EM. Structure 2019, 27 (12) , 1862-1874.e7. https://doi.org/10.1016/j.str.2019.10.004
- Javier García-Nafría, Christopher G. Tate. Cryo-EM structures of GPCRs coupled to Gs, Gi and Go. Molecular and Cellular Endocrinology 2019, 488 , 1-13. https://doi.org/10.1016/j.mce.2019.02.006
- Sebastian Raschka. Automated discovery of GPCR bioactive ligands. Current Opinion in Structural Biology 2019, 55 , 17-24. https://doi.org/10.1016/j.sbi.2019.02.011
- Yi-Lynn Liang, Maryam Khoshouei, Giuseppe Deganutti, Alisa Glukhova, Cassandra Koole, Thomas S. Peat, Mazdak Radjainia, Jürgen M. Plitzko, Wolfgang Baumeister, Laurence J. Miller, Deborah L. Hay, Arthur Christopoulos, Christopher A. Reynolds, Denise Wootten, Patrick M. Sexton. Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor. Nature 2018, 561 (7724) , 492-497. https://doi.org/10.1038/s41586-018-0535-y