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.   Y. Kang and L. Chen. Structural basis for the binding of DNP and purine nucleotides onto UCP1. in Nature, 2023, 2023/06/20 edn Vol. 620 226-231.

2.      Y. Yang and L. Chen. Functional dissection of KATP channel structures reveals the importance of a conserved interface. in Structure, 2023, 20231201 edn.

3.      D. Ding, T. Hou, M. Wei, J. X. Wu and L. Chen. The inhibition mechanism of the SUR2A-containing K(ATP) channel by a regulatory helix. in Nat Commun, 2023, 2023/06/18 edn Vol. 14 3608.

4.      W. Cui, Y. Niu, Z. Sun, R. Liu and L. Chen. Structures of human SGLT in the occluded state reveal conformational changes during sugar transport. in Nat Commun, 2023, 2023/05/23 edn Vol. 14 2920.

5.      R. Liu, Y. Kang and L. Chen. NO binds to the distal site of haem in the fully activated soluble guanylate cyclase. in Nitric Oxide, 2023, 2023/03/28 edn Vol. 134-135 17-22.

6.      R. Liu, K. Song, J. X. Wu, X. P. Geng, L. Zheng, X. Gao, H. Peng and L. Chen. Structure of human phagocyte NADPH oxidase in the resting state. in Elife, 2022, 2022/11/23 edn Vol. 11.

7.      Y. Niu, W. Cui, R. Liu, S. Wang, H. Ke, X. Lei and L. Chen. Structural mechanism of SGLT1 inhibitors. in Nat Commun, 2022, 2022/10/29 edn Vol. 13 6440.

8.      X. He, Y. Kang and L. Chen. Identification of ASPDH as a novel NAADP-binding protein. in Biochem Biophys Res Commun, 2022, 2022/07/17 edn Vol. 621 168-175.

9.      Y. Yang, M. Wei and L. Chen. Structural identification of riluzole-binding site on human TRPC5. in Cell Discov, 2022, 2022/07/13 edn Vol. 8 67.

10.   M. Wang, J. X. Wu and L. Chen. Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide. in Front Pharmacol, 2022, 2022/07/19 edn Vol. 13 929684.

11.   D. Ding, J. X. Wu, X. Duan, S. Ma, L. Lai and L. Chen. Structural identification of vasodilator binding sites on the SUR2 subunit. in Nat Commun, 2022, 2022/05/14 edn Vol. 13 2675.

12.   M. Wang, J. X. Wu, D. Ding and L. Chen. Structural insights into the mechanism of pancreatic KATP channel regulation by nucleotides. in Nat Commun, 2022, 2022/05/19 edn Vol. 13 2770.

13.   Y. Kang and L. Chen. Structure and mechanism of NALCN-FAM155A-UNC79-UNC80 channel complex. in Nat Commun, 2022, 2022/05/14 edn Vol. 13 2639.

14.   W. Guo, M. Wang and L. Chen. A co-expression vector for baculovirus-mediated protein expression in mammalian cells. in Biochem Biophys Res Commun, 2022, 2022/01/26 edn Vol. 594 69-73.

15.   W. Guo, Q. Tang, M. Wei, Y. Kang, J. X. Wu and L. Chen. Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites. in Neuron, 2022, 2022/01/21 edn Vol. 110 1023-1035 e5.

16.   Y. Niu, R. Liu, C. Guan, Y. Zhang, Z. Chen, S. Hoerer, H. Nar and L. Chen. Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. in Nature, 2021, 2021/12/08 edn Vol. 601 280-284.

17.   R. Liu, Y. Kang and L. Chen. Activation mechanism of human soluble guanylate cyclase by stimulators and activators. in Nat Commun, 2021, Vol. 12 5492.

18.   K. Song, M. Wei, W. Guo, L. Quan, Y. Kang, J. X. Wu and L. Chen. Structural basis for human TRPC5 channel inhibition by two distinct inhibitors. in Elife, 2021, 2021/03/09 edn Vol. 10.

19.   J. X. Wu, R. Liu, K. Song and L. Chen. Structures of human dual oxidase 1 complex in low-calcium and high-calcium states. in Nat Commun, 2021, 2021/01/10 edn Vol. 12 155.

20.   C. Guan, Y. Niu, S. C. Chen, Y. Kang, J. X. Wu, K. Nishi, C. C. Y. Chang, T. Y. Chang, T. Luo and L. Chen. Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor. in Nat Commun, 2020, 2020/05/20 edn Vol. 11 2478.

21.   Y. Kang, J. X. Wu and L. Chen. Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex. in Nat Commun, 2020, 2020/12/05 edn Vol. 11 6199.

22.   J. X. Wu and L. Chen. Recent Progress on The Studies of OSCA/TMEM63 Family Ion Channels. in Progress in Biochemistry and Biophysics, 2020, Vol. 47 123-130.

23.   Y. Kang, R. Liu, J. X. Wu and L. Chen. Structural insights into the mechanism of human soluble guanylate cyclase. in Nature, 2019, 2019/09/13 edn Vol. 574 206-210.

24.   W. Guo and L. Chen. Recent progress in structural studies on canonical TRP ion channels. in Cell Calcium, 2019, 2019/09/07 edn Vol. 83 102075.

25.   D. Ding, M. Wang, J. X. Wu, Y. Kang and L. Chen. The Structural Basis for the Binding of Repaglinide to the Pancreatic KATP Channel. in Cell Rep, 2019, 2019/05/09 edn Vol. 27 1848-1857 e4.

26.   M. Zhang, D. Wang, Y. Kang, J. X. Wu, F. Yao, C. Pan, Z. Yan, C. Song and L. Chen. Structure of the mechanosensitive OSCA channels. in Nat Struct Mol Biol, 2018, 2018/09/08 edn Vol. 25 850-858.

27.   J. X. Wu, D. Ding, M. Wang, Y. Kang, X. Zeng and L. Chen. Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels. in Protein Cell, 2018, 2018/03/30 edn Vol. 9 553-567.

28.   Q. Tang, W. Guo, L. Zheng, J. X. Wu, M. Liu, X. Zhou, X. Zhang and L. Chen. Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. in Cell Research, 2018, 2018/04/28 edn Vol. 28 746-755.

29.   N. Li, J. X. Wu, D. Ding, J. Cheng, N. Gao and L. Chen. Structure of a Pancreatic ATP-Sensitive Potassium Channel. in Cell, 2017, 2017/01/14 edn Vol. 168 101-110 e10.

30.   K. L. Durr, L. Chen, R. A. Stein, R. De Zorzi, I. M. Folea, T. Walz, H. S. McHaourab and E. Gouaux. Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states. in Cell, 2014, 2014/08/12 edn Vol. 158 778-792.

31.   L. Chen, K. L. Durr and E. Gouaux. X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism. in Science, 2014, 2014/08/12 edn Vol. 345 1021-6.

32.   L. Chen, F. J. Xin, J. Wang, J. Hu, Y. Y. Zhang, S. Wan, L. S. Cao, C. Lu, P. Li, S. F. Yan, D. Neumann, U. Schlattner, B. Xia, Z. X. Wang and J. W. Wu. Conserved regulatory elements in AMPK. in Nature, 2013, 2013/06/15 edn Vol. 498 E8-10.

33.   L. Chen, J. Wang, Y. Y. Zhang, S. F. Yan, D. Neumann, U. Schlattner, Z. X. Wang and J. W. Wu. AMP-activated protein kinase undergoes nucleotide-dependent conformational changes. in Nature Structural and Molecular Biology, 2012, 2012/06/05 edn Vol. 19 716-8.

34.   L. Chen, Z. H. Jiao, L. S. Zheng, Y. Y. Zhang, S. T. Xie, Z. X. Wang and J. W. Wu. Structural insight into the autoinhibition mechanism of AMP-activated protein kinase. in Nature, 2009, 2009/05/29 edn Vol. 459 1146-9.