Contact
Faculty Assistant

Tammy Griffin
tgriffin@princeton.edu
Thomas Laboratory, 204
609-258-1694

Research Focus

Membrane transport is a vital physiological process that maintains cellular homeostasis, converts different energy forms, and generates and transduces signals. Transmembrane movement of chemicals can be achieved through diffusion, vesicular translocation, and protein-mediated facilitative diffusion or active transport. Based on the studies on representative channels, uniporters, and secondary active transporters, I seek to unveil the governing principles of membrane transport. The resolution revolution in cryo-electron microscopy (cryo-EM) has propelled structural biology into a new era.

My scientific goal as a structural biologist is to reveal the molecular choreography at atomic resolution, to unveil the physiological and cellular processes involving membrane transport (including cellular uptake of glucose, generation of action potential, and excitation-contraction coupling of muscles). In the past five years, my laboratory has made significant progress towards elucidating the structures of human glucose transporters (GLUTs) and various eukaryotic voltage-gated sodium and calcium channels (Nav and Cav). Moving forward, we aim to acquire their dynamic structures, to better comprehend how lipids modulate their activities, and to understand how disease-associated mutations cripple the normal functions of these membrane transport proteins .

In addition, we plan to determine the atomic structures of recombinantly expressed and functionally well-characterized mammalian Nav and Cav channels, in order to establish a consistent structure-function relationship. Finally, based on our previously resolve structures of endogenous Ca2+ channels (Cav1.1 and RyR1), we plan to employ cryo-electron tomography to resolve the in situ ultrastructure formed by plasma membrane-anchored Cav1.1 and sarcoplasmic reticulum-anchored RyR1, in an attempt to recapitulate excitation-contraction coupling of muscles with higher spatial and temporal resolutions. I believe that these studies will ultimately lead to the deciphering of the electromechanical coupling mechanism in cells, as well as structure-based drug discovery.

Research Areas
Chemical Biology
Honors

FAOBMB Award for Research Excellence (2018)

Wu-Janssen Award in Biomedical Basic Research, China (2017)

Teaching award, Tsinghua University (2017)

Alexander M. Cruickshank Award for the Gordon Research Conference on Membrane Transport Proteins: Molecules to Medicine (2016)

The Raymond and Beverly Sackler International Prize in Biophysics (2015)

The Protein Science Young Investigator Award the Protein Society (2015)

Cheung Kong Scholar, Ministry of Education, China (2014)

The Ho Leung Ho Lee Award for Advancement in Science and Technology, China (2014)

Promega Awards for Biochemistry (2014)

Cell “40under40” (2014)

Award for “Women in Science” of China (2012)

CC Tan Award for Innovation in Life Sciences, China (2012)

Howard Hughes Medical Institute International Early Career Scientist (2012)

National Outstanding Young Scientist Award, China (2011)

Young Scientist Award (North America Regional Winner) cosponsored by AAAS/Science and GE (2006)

 

Selected Recent Publications

Xin Gong, Hongwu Qian, Pingping Cao, Xin Zhao, Qiang Zhou, Jianlin Lei, Nieng Yan (2018) Structural basis for the recognition of Sonic Hedgehog by human Patched1. Science (Research Article), 10.1126/science.aas8935.

Juanrong Zhang, Wenzhi Mao, Yanhui Ren, Rui-Ning Sun, Nieng Yan#, and Haipeng Gong# (2018) Simulating the ion permeation and ion selection for a eukaryotic voltage-gated sodium channel NaVPaS. Protein & Cell, 9:580-5  (# indicates corresponding authors).

Nieng Yan (2017) A glimpse of membrane transport through structures - Advances in the structural biology of the GLUT glucose transporters. JMB 429:2710-2725. (commissioned review for the Special issue John Kendrew 100th Birthday).

Zhen Yan, Qiang Zhou, Lin Wang, Jianping Wu, Yanyu Zhao, Gaoxingyu Huang, Wei Peng, Huaizong Shen, Jianlin Lei, and Nieng Yan (2017) Structure of the Nav1.4-β1 complex from electric eel. Cell, 170:470-482.

Xinzhe Yu, Guanghui Yang#, Chuangye Yan, Javier Baylon, Jing Jiang, He Fan, Guifeng Lu, Kazuya Hasegawa, Hideo Okumura, Tingliang Wang, Emad Tajkhorshid, Shuo Li, and Nieng Yan# (2017) Dimeric structure of the uracil:proton symporter UraA provides mechanistic insights into the SLC4/23/26 transporters. Cell Research, 27:1020-1033 (# indicates corresponding authors).

Meng Ke, Yafei Yuan, Xin Jiang, Nieng Yan#, and Haipeng Gong# (2017) Molecular determinants for the thermodynamic and functional divergence of uniporter GLUT1 and proton symporter XylE. PLoS Computational Biology, 13:e1005603. doi: 10.1371/journal.pcbi.1005603  (# indicates corresponding authors).

Hongwu Qian, Xin Zhao, Pingping Cao, Jianlin Lei, Nieng Yan# and Xin Gong# (2017) Structure of the human lipid exporter ABCA1. Cell, 169:1228-1239 (# indicates corresponding authors).

Huaizong Shen, Qiang Zhou, Xiaojing Pan, Zhangqiang Li, Jianping Wu, and Nieng Yan (2017) Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution. Science (Research Article), 355. pii: eaal4326. [Epub ahead of print]

Weiyun Huang, Minhao Liu, S.Frank Yan, Nieng Yan (2017) Structure-based assessment of disease-related mutations in human voltage-gated sodium channels. Protein & Cell, 8:401-438.

Xin Gong, Hongwu Qian, Wei Shao, Jingxian Li, Jianping Wu, Jun-Jie Liu, Wenqi Li, Hong-Wei Wang, Peter Espenshade#, and Nieng Yan# (2016) Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization. Cell Research, 26: 1197-1211.

Wei Peng, Huaizong Shen, Jianping Wu, Wenting Guo, Xiaojing Pan, Ruiwu Wang, S. R. Wayne Chen#, and Nieng Yan# (2016) Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2. Science (Research Article), 354: pii: aah5324 (# indicates corresponding authors).

Jianping Wu, Zhen Yan, Zhangqiang Li, Xingyang Qian, Shan Lu, Mengqiu Dong, Qiang Zhou, and Nieng Yan (2016) Structure of the voltage-gated calcium channel Cav1.1 at 3.6 Å resolution. Nature (Article), 537:191-6.

Xiaochen Bai, Zhen Yan#, Jianping Wu, Zhangqiang Li, and Nieng Yan# (2016) The Central domain of RyR1 is the transducer for long-range allosteric gating of channel opening. Cell Research, 26:995-1006 (# indicates corresponding authors).

Xin Gong, Hongwu Qian, Xinhui Zhou, Jianping Wu, Tao Wan, Pingping Cao, Weiyun Huang, Xin Zhao, Xudong Wang, Peiyi Wang, Yi Shi, George F. Gao, Qiang Zhou#, and Nieng Yan# (2016) Structural insights into the Niemann-Pick C1 (NPC1)-mediated cholesterol transfer and Ebola infection. Cell, 165:1467-78 (# indicates corresponding authors).

Dong Deng#, and Nieng Yan# (2016)  GLUT, SGLT, and SWEET: Structural and mechanistic investigations of the glucose transporters. Protein Sci. 25:546-58. (commissioned review, # indicates the corresponding author).

Jianping Wu, Zhen Yan, Zhangqiang Li, Chuangye Yan, Shan Lu, Mengqiu Dong, and Nieng Yan (2015) Architecture of the voltage-gated calcium channel Cav1.1 complex. Science (Research Article), 350:aad2395. doi: 10.1126/science.aad2395.

Dong Deng, Pengcheng Sun, Chuangye Yan, Meng Ke, Xin Jiang, Lei Xiong, Wenlin Ren, Kunio Hirata, Masaki Yamamoto, Shilong Fan, Haipeng Gong, and Nieng Yan (2015) Molecular basis of ligand recognition and transport by glucose transporters. Nature (Article), 526:391-6.

Ruobing Ren, Xinhui Zhou, Yuan He, Meng Ke, Jianping Wu, Xiaohui Liu, Chuangye Yan, Yixuan Wu, Xin Gong, Xiaoguang Lei, S. Frank Yan, Arun Radhakrishnan, and Nieng Yan (2015) Crystal structure of a mycobacterial Insig homologue provides insight into how these sensors monitor sterol levels. Science, 349:187-191.

Nieng Yan (2015) Structural biology of the major facilitator superfamily transporters. Annual Review of Biophysics, 44:257-83 (commissioned review).

Xin Gong, Jingxian Li, Wei Shao, Jianping Wu, Hongwu Qian, Ruobing Ren, Peter Espenshade#, and Nieng Yan# (2015) Structure of the WD40 domain of SCAP from fission yeast reveals the molecular basis for SREBP recognition. Cell Research, 25:401-11 (# indicates corresponding authors).

Cuicui Shen, Xiang Wang, Yexing Liu, Quanxiu Li, Zhao Yang, Nieng Yan, Tingting Zou, Ping Yin. (2015) Specific RNA recognition by designer pentatricopeptide repeat protein. Molecular Plant, 8:667-70.

Zhen Yan, Xiaochen Bai, Chuangye Yan, Jianping Wu, Zhangqiang Li, Tian Xie, Wei Peng, Changcheng Yin, Xueming Li, Sjors H.W.Scheres#, Yigong Shi#, and Nieng Yan# (2014) Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. Nature (Article), 517:50-5 (# indicates corresponding authors).

Jing Wang, Chuangye Yan, Yini Li, Kunio Hirata, Masaki Yamamoto, Nieng Yan#, and Qi Hu# (2014) Crystal structure of a bacterial homologue of SWEET transporters. Cell Research, 24:1486-9 (# indicates corresponding authors).

Quanxiu Li, Chuangye Yan, Huisha Xu, Zheng Wang, Jiafu Long, Wenqi Li, Jianping Wu, Ping Yin, and Nieng Yan (2014) Examination of the Dimerization States of the Single-stranded RNA-recognition Protein PPR10. JBC, 289:31503-12.

Yuan He, Kan Wang, and Nieng Yan (2014) The recombinant expression systems for structure determination of eukaryotic membrane proteins. Protein & Cell, 5:658-72 (review).

Dong Deng, Chao Xu, Pengcheng Sun, Jianping Wu, Chuangye Yan, Mingxu Hu, and Nieng Yan (2014) Crystal structure of the human glucose transporter GLUT1. Nature (Article), 510:121-5.

Yuan He, Qi Hao, Wenqi Li, Chuangye Yan, Nieng Yan#, and Ping Yin# (2014) Identification and Characterization of ABA Receptors in Oryza sativa. PLoS ONE, 9:e95246 (# indicates corresponding authors).

Dong Deng, Chuangye Yan, Jianping Wu, Xiaojing Pan, and Nieng Yan (2014) Revisiting the TALE repeat. Protein & Cell, 5:297-306.

M. Gregor Madej, Linfeng Sun  Nieng Yan#, and  H. Ronald Kaback# (2014) Functional architecture of MFS d-glucose transporters. PNAS, 111:E719-727 (# indicates corresponding authors).

Wenqi Li, Li Wang, Xinlei Sheng, Chuangye Yan, Rui Zhou, Jing Hang, Ping Yin, and Nieng Yan (2013)  Molecular basis for the selective and ABA-independent inhibition of PP2CA by PYL13. Cell Research, 23:1369-79.

Ping Yin, Quanxiu Li, Chuangye Yan, Ying Liu, Junjie Liu, Feng Yu, Zheng Wang, Jiafu Long, Jianhua He, Hong-Wei Wang, Jiawei Wang, Jian-Kang Zhu, Yigong Shi, Nieng Yan (2013) Structural basis for the modular recognition of single-stranded RNA by PPR proteins. Nature, 504: 168-171.

Nieng Yan (2013) Structural investigation of the proton-coupled secondary transporters. Current Opinion in Structural Biology, 23: 483-91 (commissioned review).

Mengdie Xia, Huihui Liu, Yang Li, Nieng Yan, and Haipeng Gong (2013) The mechanism of Na+/K+ selectivity in mammalian voltage-gated sodium channels based on molecular dynamics simulation. Biophysics Journal, 104: 2401-9.

M. Gregor Majej, Shangyu Dang, Nieng Yan, H. Ronald Kaback (2013) Evolutionary mix-and-match with MFS transporters. PNAS, 110: 5870-5874.

Nieng Yan (2013) Structural advances for the major facilitator superfamily (MFS) transporters. Trends in Biochemical Sciences, 38: 151-159 (commissioned review).

Xu Zhang, Mengdie Xia, Yang Li, Huihui Liu, Xin Jiang, Wenlin Ren, Jianping Wu, Paul DeCaen, Feng Yu, Sheng Huang, Jianhua He, David Clapham, Nieng Yan, and Haipeng Gong (2012) Analysis of the selectivity filter of the voltage-gated sodium channel NavRh. Cell Research, 23: 409-422.

Xu Zhang, and Nieng Yan (2012). The conformational shifts of the voltage sensing domains between NavRh and NavAb. Cell Research, 23: 444-447.

Linfeng Sun, Xin Zeng, Chuangye Yan, Xiuyun Sun, Xinqi Gong, Yu Rao, and Nieng Yan (2012). Crystal structure of a bacterial homologue of glucose transporters GLUT1-4. Nature (Article), 490:361-6. (highlighted by News & Views in the same issue of Nature).

Ping Yin, Dong Deng, Chuangye Yan, Xiaojing Pan, Jianzhong Jeff Xi,  Nieng Yan, and Yigong Shi (2012). Specific DNA-RNA hybrid recognition by TAL effectors. Cell Reports, 2:707-13.

Dong Deng, Ping Yin, Chuangye Yan, Xiaojing Pan, Xinqi Gong, Shiqian Qi, Tian Xie, Magdy Mahfouz, Jian-Kang Zhu, Nieng Yan#, and Yigong Shi# (2012). Recognition of methlyated DNA by TAL effectors. Cell Research, 22:1502-4 (# indicates corresponding authors).

Junichi Sugihara, Linfeng Sun, Nieng Yan, and H. Ronald Kabacka (2012). Dynamics of the L-fucose/H+ symporter revealed by fluorescence spectroscopy. PNAS, 109:14847-51.

Xu Zhang, Wenlin Ren, Paul DeCaen, Chuangye Yan, Xiao Tao, Lin Tang, Jingjing Wang, Kazuya Hasegawa, Takashi Kumasaka, Jianhua He, Jiawei Wang, David E. Clapham, and Nieng Yan (2012). Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature, 486: 130-134.

Dong Deng, Chuangye Yan, Xiaojing Pan, Magdy Mahfouz, Jiawei Wang, Jian-Kang Zhu, Yigong Shi#, and Nieng Yan# (2012) Structural basis for the specific recognition of DNA by TAL effectors. Science, 335: 720-3 (# indicates corresponding authors; cited by the Runner-up of the 2012 Breakthrough of the Year by Science).

Tian Xie, Ruobing Ren, Yuan-Yuan Zhang, Yuxuan Pang, Chuangye Yan, Xinqi Gong, Yuan He, Wenqi Li, Di Miao, Qi Hao, Haiteng Deng, Zhixin Wang, Jia-Wei Wu, and Nieng Yan (2012) Molecular mechanism for the inhibition of a critical component in the Arabidopsis thaliana abscisic acid signal transduction pathways, SnRK2.6, by the protein phosphatase ABI1. J. Biol. Chem. 287: 794-802.

Qi Hao, Ping Yin, Wenqi Li, Li Wang Chuangye Yan, Zhaohu Lin, Jim Zhen Wu, Jiawei Wang, S. Frank Yan, and Nieng Yan (2011) The molecular Basis of ABA-independent inhibition of PP2Cs by a subclass of PYL proteins. Molecular Cell, 42: 662-672.

Feiran Lu, Shuo Li, Yang Jiang, Jing Jiang, He Fan, Guifeng Lu, Dong Deng, Shangyu Dang, Xu Zhang, Jiawei Wang, and Nieng Yan (2011) Structure and mechanism of the uracil transporter UraA. Nature, 473: 243-6.

Shangyu Dang, Linfeng Sun, Feiran Lu, Jiawei Wang, and Nieng Yan (2010) The structure of a fucose transporter in an outward-open conformation. Nature, 467: 734-8

Xiaoqiu Yuan, Ping Yin, Qi Hao, Chuangye Yan, Wenqi Li, Jiawei Wang, and Nieng Yan (2010) Single amino acid alteration between isoleucine and valine determinates the pyrabactin selectivity between PYL1 and PYL2. J. Biol. Chem. 285: 28953-8.

Qi Hao, Ping Yin, Xiaoqiu Yuan, Chuangye Yan, Wenqi Li, Jiawei Wang, and Nieng Yan (2010) Functional mechanism of the ABA agonist pyrabactin. J. Biol. Chem., 285: 28946-52.

Shiqian Qi, Yuxuan Pang, Qun Liu, Hua Li, Yexing Liu, Quan Hao, Huilin Li, Nieng Yan#, and Yigong Shi# (2009) Structure of the CED-4 Apoptosome: Insights into its Assembly and Function. Cell, 141:446-457 (# indicates corresponding authors).

Yi Wang, Yongjian Huang, Jiawei Wang, Chao Cheng, Weijiao Huang, Peilong Lu, Ya-Nan Xu, Pengye Wang, Nieng Yan#, and Yigong Shi# (2009) Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel. Nature (Article) 462: 467-472 (# indicates corresponding authors).

Ping Yin, He Fan, Qi Hao, Xiaoqiu Yuan, Di Wu, Yuxuan Pang, Chuangye Yan, Wenqi Li, Jiawei Wang, and Nieng Yan (2009) Structural insights into the mechanism of abscisic acid signaling by PYL. Nature Structural & Molecular Biology, 16:1230-1236 (Cover and “article of the month”, cited by the Runner-up of the 2012 Breakthrough of the Year by Science).