Lei Chen
Email: chenlei2016(at)pku(dot)edu(dot)cn ；
Research interest: Structural Biology
Office: Room 218, Equipment Building No.2, Peking University, Yiheyuan Road No.5, Beijing, China, Zip: 100871
Research Area:
My research aims to understand how proteins work, especially integral membrane proteins. These protein play important roles in many biological processes, such as material transport, signal transduction and catalytic reaction. Understanding how those molecules work in atomic details is essential for us to manipulate their activity and improve human health. One major focus of our lab is on the gating mechanism of ion channels which are important drug targets and implicated in human diseases. For example, the energy sensors ATP-sensitive potassium channels (KATP) can couple intracellular energy status to cell excitability and gate insulin release in pancreatic beta cells. We are currently using structural biology tools combined with biochemistry and electrophysiology methods to elucidate how those channels work.
Selected Publications:
[1] Guo, W., Tang, Q., Wei, M., Kang, Y., Wu, J. X., and Chen, L. (2022) Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites, Neuron.
[2] Niu, Y., Liu, R., Guan, C., Zhang, Y., Chen, Z., Hoerer, S., Nar, H., and Chen, L. (2021) Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter, Nature 601, 280-284.
[3] Liu, R., Kang, Y., and Chen, L. (2021) Activation mechanism of human soluble guanylate cyclase by stimulators and activators, Nat Commun 12, 5492.
[4] Song, K., Wei, M., Guo, W., Quan, L., Kang, Y., Wu, J. X., and Chen, L. (2021) Structural basis for human TRPC5 channel inhibition by two distinct inhibitors, Elife 10.
[5] Wu, J. X., Liu, R., Song, K., and Chen, L. (2021) Structures of human dual oxidase 1 complex in low-calcium and high-calcium states, Nat Commun 12, 155.
[6] Guan, C., Niu, Y., Chen, S. C., Kang, Y., Wu, J. X., Nishi, K., Chang, C. C. Y., Chang, T. Y., Luo, T., and Chen, L. (2020) Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor, Nat Commun 11, 2478.
[7] Kang, Y., Wu, J. X., and Chen, L. (2020) Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex, Nat Commun 11, 6199.
[8] Wu, J. X., Ding, D., Wang, M., and Chen, L. (2020) Structural Insights into the Inhibitory Mechanism of Insulin Secretagogues on the Pancreatic ATP-Sensitive Potassium Channel, Biochemistry (Mosc.) 59, 18-25.
[9] Kang, Y., Liu, R., Wu, J. X., and Chen, L. (2019) Structural insights into the mechanism of human soluble guanylate cyclase, Nature 574, 206-210.
[10] Guo, W., and Chen, L. (2019) Recent progress in structural studies on canonical TRP ion channels, Cell Calcium 83, 102075.
[11] Ding, D., Wang, M., Wu, J. X., Kang, Y., and Chen, L. (2019) The Structural Basis for the Binding of Repaglinide to the Pancreatic KATP Channel, Cell Rep 27, 1848-1857 e1844.
[12] Zhang, M., Wang, D., Kang, Y., Wu, J. X., Yao, F., Pan, C., Yan, Z., Song, C., and Chen, L. (2018) Structure of the mechanosensitive OSCA channels, Nat. Struct. Mol. Biol. 25, 850-858.
[13] Wu, J. X., Ding, D., Wang, M., Kang, Y., Zeng, X., and Chen, L. (2018) Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels, Protein Cell 9, 553-567.
[14] Tang, Q., Guo, W., Zheng, L., Wu, J. X., Liu, M., Zhou, X., Zhang, X., and Chen, L. (2018) Structure of the receptor-activated human TRPC6 and TRPC3 ion channels, Cell Res. 28, 746-755.
[15] Li, N., Wu, J. X., Ding, D., Cheng, J., Gao, N., and Chen, L. (2017) Structure of a Pancreatic ATP-Sensitive Potassium Channel, Cell 168, 101-110 e110.
[16] Durr, K. L., Chen, L., Stein, R. A., De Zorzi, R., Folea, I. M., Walz, T., McHaourab, H. S., and Gouaux, E. (2014) Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states, Cell 158, 778-792.
[17] Chen, L., Durr, K. L., and Gouaux, E. (2014) X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism, Science345, 1021-1026.
[18] Chen, L., Xin, F. J., Wang, J., Hu, J., Zhang, Y. Y., Wan, S., Cao, L. S., Lu, C., Li, P., Yan, S. F., Neumann, D., Schlattner, U., Xia, B., Wang, Z. X., and Wu, J. W. (2013) Conserved regulatory elements in AMPK, Nature 498, E8-10.
[19] Chen, L., Wang, J., Zhang, Y. Y., Yan, S. F., Neumann, D., Schlattner, U., Wang, Z. X., and Wu, J. W. (2012) AMP-activated protein kinase undergoes nucleotide-dependent conformational changes, Nat. Struct. Mol. Biol. 19, 716-718.
[20] Chen, L., Jiao, Z. H., Zheng, L. S., Zhang, Y. Y., Xie, S. T., Wang, Z. X., and Wu, J. W. (2009) Structural insight into the autoinhibition mechanism of AMP-activated protein kinase, Nature 459, 1146-1149.
