Our major research program focuses on the structural and functional studies of receptor tyrosine kinases (RTKs), a family of cell surface receptors that play a key role in regulating normal cellular processes. Defects in RTK activation are causative in many cancers and other diseases and are targeted by many drugs. To date, many crystal structures for individual domains of RTKs are available. However, structural information on full-length RTKs, either in their apo- or ligand-bound multimeric states, has been elusive because these elongated and conformationally dynamic single-pass transmembrane proteins are difficult to crystalize. Thus, the central question of how information is relayed across plasma membrane by these important proteins remains unanswered. The RTK complexes have a molecular weight ranging from 140kDa to 800kDa, which makes them suitable for cryo-EM structural determination. Our lab is currently working on several members of RTK, including EGFR, RET, IR, and IGF1R. Solving the structures of different members of the RTK family will reveal similarities and differences in the structure-function relationships within this receptor family.

Collaborators

Xuewu Zhang, Hongtao Yu, Eunhee Choi

Related Publications

Liwei Wang*, Catherine Hall*, Jie Li, Eunhee Choi†, Xiao-chen Bai†. Structural basis of the alkaline pH-dependent activation of insulin receptor-related receptor. Nature Structural & Molecular Biology. 2023.

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Guipeun Kang*, Corey AH Allard*, Wendy A Valencia-Montoya*, Lena van Giesen, Jeong Joo Kim, Peter B Kilian, Xiao-chen Bai, Nicholas W Bellono†, Ryan E Hibbs†. Sensory specializations drive octopus and squid behaviour. Nature. 2023.

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Shun Liu*, Hua Chen*, Yan Yin*, Defen Lu, Guoming Gao, Jie Li, Xiao-chen Bai†, Xuewu Zhang†. Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold. Science Advances. 2023.

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Eunhee Choi†, Xiao-chen Bai†. The Activation Mechanism of the Insulin Receptor: A Structural Perspective. Annual Review of Biochemistry. 2023.

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Jie Li, Jiayi Wu, Catherine Hall, Xiao-chen Bai†, Eunhee Choi†. Molecular basis for the role of disulfide-linked αCTs in the activation of insulin-like growth factor 1 receptor and insulin receptor. eLife. 2022.

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Junhee Park*, Jie Li*, John P Mayer, Kerri A Ball, Jiayi Wu, Catherine Hall, Domenico Accili, Michael HB Stowell, Xiao-chen Bai†, Eunhee Choi†. Activation of the insulin receptor by an insulin mimetic peptide. Nature Communications. 2022.

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Phong T Nguyen†, Christine Deisl, Michael Fine, Trevor S Tippetts, Emiko Uchikawa, Xiao-chen Bai†, Beth Levine. Structural basis for gating mechanism of the human sodium-potassium pump. Nature Communications. 2022.

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Yan Fang*, Pengcheng Sun*, Xuping Xie, Mingjian Du, Fenghe Du, Jianfeng Ye, Birte K Kalveram, Jessica A Plante, Kenneth S Plante, Bo Li, Xiao-chen Bai, Pei-Yong Shi†, Zhijian J Chen†. An antibody that neutralizes SARS-CoV-1 and SARS-CoV-2 by binding to a conserved spike epitope outside the receptor binding motif. Science immunology. 2022.

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Jie Li, Junhee Park, John P. Mayer, Kristofor J. Webb, Emiko Uchikawa, Jiayi Wu, Shun Liu, Xuewu Zhang, Michael H.B. Stowell†, Eunhee Choi†, Xiao-chen Bai†. Synergistic activation of the insulin receptor via two distinct sites. Nature Structural & Molecular Biology. 2022.

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Defen Lu*, Guijun Shang*, Jie Li , Yong Lu , Xiao-chen Bai†, Xuewu Zhang†. Activation of human STING by targeting a pocket in the transmembrane domain. Nature. 2022.

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Kai Cai, Xuewu Zhang†, Xiao-chen Bai†. Cryo-electron Microscopic Analysis of Single-Pass Transmembrane Receptors. Chemical Reviews. 2022.

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Karolina P Stepien, Junjie Xu, Xuewu Zhang, Xiao-chen Bai†, Josep Rizo†. SNARE assembly enlightened by cryo-EM structures of a synaptobrevin-Munc18-1-syntaxin-1 complex. Science Advances. 2022.

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Jie Yin*, Yanyong Kang*, Aaron P McGrath*, Karen Chapman, Megan Sjodt, Eiji Kimura, Atsutoshi Okabe, Tatsuki Koike, Yuhei Miyanohana, Yuji Shimizu, Rameshu Rallabandi, Peng Lian, Xiao-chen Bai, Mack Flinspach†, Jef K De Brabander†, Daniel M Rosenbaum†. Molecular mechanism of the wake-promoting agent TAK-925. Nature communications. 2022

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Venkatesh P Mysore*, Zhi-Wei Zhou*, Chiara Ambrogio*, Lianbo Li, Jonas N Kapp, Chunya Lu, Qi Wang, Maxwell R Tucker, Jeffrey J Okoro, Gabriela Nagy-Davidescu, Xiao-chen Bai, Andreas Plückthun, Pasi A Jänne, Kenneth D Westover, Yibing Shan†, David E Shaw†. A structural model of a Ras–Raf signalosome. Nature Structural & Molecular Biology. 2021.

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Hailong Yu, Xiao-Chen Bai, Weiwei Wang†. Characterization of the subunit composition and structure of adult human glycine receptors. Neuron. 2021.

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Daniel L Kober, Arun Radhakrishnan†, Joseph L Goldstein, Michael S Brown, Lindsay D Clark, Xiao-chen Bai†, Daniel M Rosenbaum†. Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing. Cell. 2021 Jul 8;184(14):3689-3701.e22.

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Emiko Uchikawa, Zhiming Chen, Guan-Yu Xiao, Xuewu Zhang†, Xiao-chen Bai†. Structural basis of the activation of c-MET receptor. Nature Communications. 2021 Jul 1;12(1):4074.

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Defen Lu, Guijun Shang, Xiaojing He, Xiao-chen Bai†, Xuewu Zhang†. Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex. Nature Communications. 2021 May 26;12(1):3172.

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Xiao-chen Bai†. Seeing Atoms by Single-Particle Cryo-EM. Trends in Biochemical Sciences. 2021 Apr;46(4):253-254.

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Byung-Cheon Jeong, Sung Jun Bae, Lisheng Ni, Xuewu Zhang, Xiao-chen Bai†, Xuelian Luo†. Cryo-EM structure of the Hippo signaling integrator human STRIPAK. Nature Structural & Molecular Biology. 2021 Mar;28(3):290-299.

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Jie Yin, Kuang-Yui M Chen, Mary J Clark, Mahdi Hijazi, Punita Kumari, Xiao-chen Bai, Roger K Sunahara, Patrick Barth, Daniel M Rosenbaum. Structure of a D2 dopamine receptor–G-protein complex in a lipid membrane. Nature. 2020. Aug;584(7819):125-129.

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Yan Wang, Yan Han, Ji She, Nam X Nguyen, Vamsi K Mootha, Xiao-chen Bai, Youxing Jiang. Structural insights into the Ca²⁺-dependent gating of the human mitochondrial calcium uniporter. eLife. 2020. Aug 7;9.

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Matthew Bratkowski, Tian Xie, Desiree A Thayer, Shradha Lad, Prakhyat Mathur, Yu-San Yang, Gregory Danko, Thomas C Burdett, Jean Danao, Aaron Cantor, Jennifer A Kozak, Sean P Brown, Xiaochen Bai, Shilpa Sambashivan. Structural and mechanistic regulation of the Pro-degenerative NAD hydrolase SARM1. Cell Reports. 2020. Aug 4;32(5):107999.

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Jing Xue, Tian Xie, Weizhong Zeng, Youxing Jiang†, Xiao-chen Bai†. Cryo-EM structures of human ZnT8 in both outward- and inward-facing conformations. eLife. 2020. Jul 29;9.

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Xuewu Zhang†, Xiao-chen Bai†, Zhijian J Chen†. Structures and Mechanisms in the cGAS-STING Innate Immunity Pathway. Immunity. 2020. Jul 14;53(1):43-53.

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Zhubing Shi, Haishan Gao, Xiao-chen Bai†, Hongtao Yu†. Cryo-EM structure of the human cohesin-NIPBL-DNA complex. Science. 2020. Jun 26;368(6498):1454-1459.

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Si Liu, Shenghai Chang, Binming Han, Lingyi Xu, Mingfeng Zhang, Cheng Zhao, Wei Yang, Feng Wang, Jingyuan Li†, Eric Delpire†, Sheng Ye†, Xiao-chen Bai†, Jiangtao Guo†. Cryo-EM structures of the human cation-chloride cotransporter KCC1. Science. 2019. Oct 25;366(6464):505-508.

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Jie Li*, Eunhee Choi*†, Hongtao Yu†, Xiao-chen Bai†. Structural basis of the activation of type 1 insulin-like growth factor receptor. Nature Communications 2019;10 (1), 1-11

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Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands
Jie Li*, Guijun Shang*, Yu-Ju Chen, Chad A Brautigam, Jen Liou, Xuewu Zhang†, Xiao-chen Bai†, eLife 2019;8: e47650.

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Emiko Uchikawa*, Eunhee Choi†*, Guijun Shang , Hongtao Yu†, Xiao-chen Bai†. Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex. eLife 2019;8:e48630.

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