Nieng Yan

Contact
nyan@princeton.eduFaculty Assistant
A.J. MaziarskiEducation
- Ph.D., Molecular Biology, Princeton University
- B.S., Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China
Research Area
Biochemistry, Biophysics & Structural BiologyResearch Focus
Structural and chemical basis for membrane transport and lipid metabolismMembrane 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.
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Structural Basis of the Modulation of the Voltage-Gated Calcium Ion Channel Ca 1.1 by Dihydropyridine Compounds*. Angew Chem Int Ed Engl. 2020 ;. .
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Structural Basis for Blocking Sugar Uptake into the Malaria Parasite Plasmodium falciparum. Cell. 2020 ;183(1):258-268.e12. .
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Structural Basis of Low-pH-Dependent Lysosomal Cholesterol Egress by NPC1 and NPC2. Cell. 2020 ;182(1):98-111.e18. .
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Structural basis of ion transport and inhibition in ferroportin. Nat Commun. 2020 ;11(1):5686. .
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Cryo-EM analysis of a membrane protein embedded in the liposome. Proc Natl Acad Sci U S A. 2020 ;117(31):18497-18503. .
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Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated Na channels in nanodisc. Proc Natl Acad Sci U S A. 2020 ;117(25):14187-14193. .
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Structural basis for catalysis and substrate specificity of human ACAT1. Nature. 2020 ;581(7808):333-338. .
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Structure and mechanism of human diacylglycerol O-acyltransferase 1. Nature. 2020 ;581(7808):329-332. .
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High-yield monolayer graphene grids for near-atomic resolution cryoelectron microscopy. Proc Natl Acad Sci U S A. 2020 ;117(2):1009-1014. .
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Structures of human Na1.7 channel in complex with auxiliary subunits and animal toxins. Science. 2019 ;363(6433):1303-1308. .
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Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators. Proc Natl Acad Sci U S A. 2019 ;116(51):25575-25582. .
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Cryo-EM structures of apo and antagonist-bound human Ca3.1. Nature. 2019 ;576(7787):492-497. .
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Modulation of cardiac ryanodine receptor 2 by calmodulin. Nature. 2019 ;572(7769):347-351. .
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Molecular Basis for Ligand Modulation of a Mammalian Voltage-Gated Ca Channel. Cell. 2019 ;177(6):1495-1506.e12. .
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Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm. Nat Commun. 2019 ;10(1):2320. .
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Molecular basis for pore blockade of human Na channel Na1.2 by the μ-conotoxin KIIIA. Science. 2019 ;363(6433):1309-1313. .
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The shape of human squalene epoxidase expands the arsenal against cancer. Nat Commun. 2019 ;10(1):888. .
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Human SEIPIN Binds Anionic Phospholipids. Dev Cell. 2018 ;47(2):248-256.e4. .
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Structural basis for the modulation of voltage-gated sodium channels by animal toxins. Science. 2018 ;362(6412). .
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Structure of the human voltage-gated sodium channel Na1.4 in complex with β1. Science. 2018 ;362(6412). .
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Structural basis for the recognition of Sonic Hedgehog by human Patched1. Science. 2018 ;361(6402). .
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Simulating the ion permeation and ion selection for a eukaryotic voltage-gated sodium channel NaPaS. Protein Cell. 2018 ;9(6):580-585. .
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Crystallization and Structural Determination of the Human Glucose Transporters GLUT1 and GLUT3. Methods Mol Biol. 2018 ;1713:15-29. .
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Structure of the Human Lipid Exporter ABCA1. Cell. 2017 ;169(7):1228-1239.e10. .
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Molecular determinants for the thermodynamic and functional divergence of uniporter GLUT1 and proton symporter XylE. PLoS Comput Biol. 2017 ;13(6):e1005603. .
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Structure of the Na1.4-β1 Complex from Electric Eel. Cell. 2017 ;170(3):470-482.e11. .
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Dimeric structure of the uracil:proton symporter UraA provides mechanistic insights into the SLC4/23/26 transporters. Cell Res. 2017 ;27(8):1020-1033. .
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A Glimpse of Membrane Transport through Structures-Advances in the Structural Biology of the GLUT Glucose Transporters. J Mol Biol. 2017 ;429(17):2710-2725. .
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Structure-based assessment of disease-related mutations in human voltage-gated sodium channels. Protein Cell. 2017 ;8(6):401-438. .
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Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution. Science. 2017 ;355(6328). .
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Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization. Cell Res. 2016 ;26(11):1197-1211. .
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GLUT, SGLT, and SWEET: Structural and mechanistic investigations of the glucose transporters. Protein Sci. 2016 ;25(3):546-58. .
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Crystal structure of a LacY-nanobody complex in a periplasmic-open conformation. Proc Natl Acad Sci U S A. 2016 ;113(44):12420-12425. .
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Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2. Science. 2016 ;354(6310). .
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The Central domain of RyR1 is the transducer for long-range allosteric gating of channel opening. Cell Res. 2016 ;26(9):995-1006. .
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Molecular basis of ligand recognition and transport by glucose transporters. Nature. 2015 ;526(7573):391-6. .
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PROTEIN STRUCTURE. Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels. Science. 2015 ;349(6244):187-91. .
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Hopes for the year ahead. Nature. 2015 ;517(7532):111-3. .
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Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. Nature. 2015 ;517(7532):50-55. .
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Structure of the voltage-gated calcium channel Cav1.1 complex. Science. 2015 ;350(6267):aad2395. .
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Structure of the WD40 domain of SCAP from fission yeast reveals the molecular basis for SREBP recognition. Cell Res. 2015 ;25(4):401-11. .
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Specific RNA recognition by designer pentatricopeptide repeat protein. Mol Plant. 2015 ;8(4):667-70. .
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Structural Biology of the Major Facilitator Superfamily Transporters. Annu Rev Biophys. 2015 ;44:257-83. .
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The recombinant expression systems for structure determination of eukaryotic membrane proteins. Protein Cell. 2014 ;5(9):658-72. .
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Examination of the dimerization states of the single-stranded RNA recognition protein pentatricopeptide repeat 10 (PPR10). J Biol Chem. 2014 ;289(45):31503-12. .
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Crystal structure of the human glucose transporter GLUT1. Nature. 2014 ;510(7503):121-5. .
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Functional architecture of MFS D-glucose transporters. Proc Natl Acad Sci U S A. 2014 ;111(7):E719-27. .
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Crystal structure of a bacterial homologue of SWEET transporters. Cell Res. 2014 ;24(12):1486-9. .
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Revisiting the TALE repeat. Protein Cell. 2014 ;5(4):297-306. .
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Identification and characterization of ABA receptors in Oryza sativa. PLoS One. 2014 ;9(4):e95246. .
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Structural advances for the major facilitator superfamily (MFS) transporters. Trends Biochem Sci. 2013 ;38(3):151-9. .
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Analysis of the selectivity filter of the voltage-gated sodium channel Na(v)Rh. Cell Res. 2013 ;23(3):409-22. .
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The conformational shifts of the voltage sensing domains between Na(v)Rh and Na(v)Ab. Cell Res. 2013 ;23(3):444-7. .
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The mechanism of Na⁺/K⁺ selectivity in mammalian voltage-gated sodium channels based on molecular dynamics simulation. Biophys J. 2013 ;104(11):2401-9. .
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Structural basis for the modular recognition of single-stranded RNA by PPR proteins. Nature. 2013 ;504(7478):168-71. .
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Molecular basis for the selective and ABA-independent inhibition of PP2CA by PYL13. Cell Res. 2013 ;23(12):1369-79. .
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Structural investigation of the proton-coupled secondary transporters. Curr Opin Struct Biol. 2013 ;23(4):483-91. .
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Evolutionary mix-and-match with MFS transporters. Proc Natl Acad Sci U S A. 2013 ;110(15):5870-4. .
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Dynamics of the L-fucose/H+ symporter revealed by fluorescence spectroscopy. Proc Natl Acad Sci U S A. 2012 ;109(37):14847-51. .
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Specific DNA-RNA hybrid recognition by TAL effectors. Cell Rep. 2012 ;2(4):707-13. .
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Crystal structure of a bacterial homologue of glucose transporters GLUT1-4. Nature. 2012 ;490(7420):361-6. .
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Recognition of methylated DNA by TAL effectors. Cell Res. 2012 ;22(10):1502-4. .
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Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature. 2012 ;486(7401):130-4. .
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Structural basis for sequence-specific recognition of DNA by TAL effectors. Science. 2012 ;335(6069):720-3. .
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The molecular basis of ABA-independent inhibition of PP2Cs by a subclass of PYL proteins. Mol Cell. 2011 ;42(5):662-72. .
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Structure and mechanism of the uracil transporter UraA. Nature. 2011 ;472(7342):243-6. .
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Single amino acid alteration between valine and isoleucine determines the distinct pyrabactin selectivity by PYL1 and PYL2. J Biol Chem. 2010 ;285(37):28953-8. .
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Functional mechanism of the abscisic acid agonist pyrabactin. J Biol Chem. 2010 ;285(37):28946-52. .
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Structure of a fucose transporter in an outward-open conformation. Nature. 2010 ;467(7316):734-8. .
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Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell. 2010 ;141(3):446-57. .
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Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel. Nature. 2009 ;462(7272):467-72. .
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Structural insights into the mechanism of abscisic acid signaling by PYL proteins. Nat Struct Mol Biol. 2009 ;16(12):1230-6. .
Dr. Nieng Yan received her B.S. degree from the Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing, China, in 2000. She then pursued her PhD in the Department of Molecular Biology at Princeton University under the supervision of Prof. Yigong Shi between 2000 and 2004. She was the regional winner of the Young Scientist Award (North America) co-sponsored by Science/AAAS and GE Healthcare in 2005 for her thesis on the structural and mechanistic study of programmed cell death. She continued her postdoctoral training at Princeton University, focusing on the structural characterization of intramembrane proteases. In 2007, she joined the faculty of School of Medicine, Tsinghua University. Her lab has been mainly focusing on the structural and functional study of membrane transport proteins exemplified by the glucose transporters and Na+/Ca2+ channels. In 2012 and 2013, she was promoted to tenured professor and Bayer Endowed Chair Professor, respectively. Dr. Yan was an HHMI international early career scientist in 2012-2017, the recipient of the 2015 Protein Society Young Investigator Award and the 2015 Beverley & Raymond Sackler International Prize in Biophysics, and the Alexander M. Cruickshank lecturer at the GRC on membrane transport proteins in 2016.
2019
- Weizmann Women & Science Award, Weizmann Institute of Science
2018
- FAOBMB Award for Excellence, Federation of National Societies of Biochemistry and Molecular Biology in the Asian and Oceanian Region
2015
- The Protein Science Young Investigator Award , Protein Society
- The Raymond and Beverly Sackler International Prize in Biophysics, Tel Aviv University
2014
- Cell "40under40", Cell
- Promega Awards for Biochemistry, Promega
2012
- Howard Hughes Medical Institute International Early Career Scientist , HHMI
2006
- Young Scientist Award (North America Regional Winner) , AAAS/Science and GE