Jue Chen (scientist) explained

Jue Chen
Birth Place:	China
Citizenship:	United States
Workplaces:	Purdue University
Alma Mater:	Harvard University
Known For:	Structural studies of ABC transporters
Spouses:	)--> Roderick MacKinnon (2017-)

Jue Chen is a Chinese-born American structural biologist and biochemist. She is the William E. Ford professor of biochemistry and head of the Laboratory of Membrane Biology and Biophysics at the Rockefeller University and a Howard Hughes Medical Institute investigator. Her research focuses on elucidating the structure and function of ATP-binding cassette (ABC) transporters.

Early life and education

Chen was born in Changsha, China and graduated from Changsha No. 1 High School in 1988. She studied at Tongji University in Shanghai before moving to the United States.^{[1] [2]}

She earned a bachelor's degree in chemistry from Ohio University in 1993, and went on to pursue PhD in biochemistry from Harvard University in 1998 under the mentorship of Don C. Wiley,^[3] where she discovered unique structural features of the influenza virus responsible for infection ^{[4] [5] [6]}

Career

Chen remained in Don C. Wiley's lab as a postdoctoral researcher before moving on to a postdoctoral fellowship at Baylor College of Medicine from 1999 to 2001 in the lab of Florante A. Quiocho, where she started studying the ATP binding cassette transporters^[7]

In 2002, Chen became an assistant professor at Purdue University where she won a number of teaching awards and published her research in high impact journals.^[8] In 2007, Chen was promoted to associate professor and subsequently, professor in 2011. In 2003 she was named a Pew Scholar and a Howard Hughes Medical Institute Investigator in 2008 ^[9] In 2014, she moved to The Rockefeller University,^[10] where she is now the William E. Ford Professor and Head of Laboratory of Membrane Biology and Biophysics.^[11]

In 2019, she was elected to the National Academy of Sciences.^[12]

Research

Chen is known for doing meaningful work in the fields of membrane biology and biophysics. She has published notable works in the fields of crystallography, intracellular transport, and, most recently, ATP-Binding Cassette Transporters and their roles in immune systems and disease. Her work on ABC transporters includes investigating their role in resistance to chemotherapy drugs; antigen presentation in adaptive immunity and viral infection; cystic fibrosis; and bacterial nutrition.

Visualizing maltose through crystallography

She has also been using crystallography to visualize how the maltose transporter protein converts the chemical energy of ATP hydrolysis into mechanical work through a series of conformational changes. This work applies specifically to bacterial cells, but has implications for humans.^[13]

ATP-binding cassette (ABC) transporters and P-glycoprotein and MRP1

Chen’s interests have recently shifted to ABC transporters involved in the immune system and disease. These are a diverse group of membrane proteins utilizing the chemical energy of ATP hydrolysis to transport substrates against their electrochemical gradients. Her initial work with ABC transporters focused on two such transporters, P-glycoprotein and MRP1. This initial work has led to new insights into a mechanism by which some cancer cells mount resistance to chemotherapy. Discovered in the 1970s, P-glycoprotein recognizes an array of structurally related compounds and pumps them out of the cell. It plays a Jekyll-and-Hyde role in human health: When the cell in question is cancerous and the compounds are therapies targeting some aspect of the cell’s internal machinery, P-glycoprotein’s action reduces the effectiveness of chemotherapy.^[14]

ATP-binding cassette (ABC) transporters and CFTR

Chen's current research focuses on ABC transporters and their roles in, specifically, cystic fibrosis. Among the thousands of ABC transporters, one member, the cystic fibrosis transmembrane conductance regulator (CFTR), has evolved to function as an ATP-gated ion channel. Mutation of the CFTR gene causes cystic fibrosis (CF), a lethal disease with a prevalence of 1 in 2500 in Caucasian populations. ^[15]

Awards and honors

• Pew Scholar (2003)
• Anatrace Membrane Protein Award, Biophysical Society (2018)
• US National Academy of Sciences (2019)^[16]

Selected works

Source:^[17]

• A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle. J Chen, G Lu, J Lin, AL Davidson, FA Quiocho. Molecular cell 12 (3), 651-661
• ATP-binding cassette transporters in bacteria. AL Davidson, J Chen. Annual review of biochemistry 73 (1), 241-268
• ATP hydrolysis is required to reset the ATP-binding cassette dimer into the resting-state conformation. G Lu, JM Westbrooks, AL Davidson, J Chen. Proceedings of the National Academy of Sciences 102 (50), 17969-17974
• Crystal structure of the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein dimerization domain reveals evolutionary linkage between corona-and arteriviridae. IM Yu, ML Oldham, J Zhang, J Chen. Journal of Biological Chemistry 281 (25), 17134-17139
• Crystal structure of a catalytic intermediate of the maltose transporter. ML Oldham, D Khare, FA Quiocho, AL Davidson, J Chen. Nature 450 (7169), 515-521
• Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase. J Diao, Y Zhang, JM Huibregtse, D Zhou, J Chen. Nature structural & molecular biology 15 (1), 65-70
• The flavivirus precursor membrane-envelope protein complex: structure and maturation. L Li, SM Lok, IM Yu, Y Zhang, RJ Kuhn, J Chen, MG Rossmann. Science 319 (5871), 1830-1834
• Structure of the immature dengue virus at low pH primes proteolytic maturation. IM Yu, W Zhang, HA Holdaway, L Li, VA Kostyuchenko, PR Chipman, ... Science 319 (5871), 1834-1837
• Structure, function, and evolution of bacterial ATP-binding cassette systems. AL Davidson, E Dassa, C Orelle, J Chen. Microbiology and molecular biology reviews 72 (2), 317-364
• Structural insights into ABC transporter mechanism. ML Oldham, AL Davidson, J Chen. Current opinion in structural biology 18 (6), 726-733
• Alternating access in maltose transporter mediated by rigid-body rotations. D Khare, ML Oldham, C Orelle, AL Davidson, J Chen. Molecular cell 33 (4), 528-536
• Association of the pr peptides with dengue virus at acidic pH blocks membrane fusion. IM Yu, HA Holdaway, PR Chipman, RJ Kuhn, MG Rossmann, J Chen. Journal of virology 83 (23), 12101-12107
• Structure and function of a HECT domain ubiquitin‐binding site. HC Kim, AM Steffen, ML Oldham, J Chen, JM Huibregtse. EMBO reports 12 (4), 334-341
• Crystal structure of the maltose transporter in a pretranslocation intermediate state. ML Oldham, J Chen. Science 332 (6034), 1202-1205
• Snapshots of the maltose transporter during ATP hydrolysis. ML Oldham, J Chen. Proceedings of the National Academy of Sciences 108 (37), 15152-15156
• Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. MS Jin, ML Oldham, Q Zhang, J Chen. Nature 490 (7421), 566-569
• Carbon catabolite repression of the maltose transporter revealed by X-ray crystallography. S Chen, ML Oldham, AL Davidson, J Chen. Nature 499 (7458), 364-368
• Molecular mechanism of the Escherichia coli maltose transporter. J Chen. Current opinion in structural biology 23 (4), 492-498
• Crystal structures of a polypeptide processing and secretion transporter. DY Lin, S Huang, J Chen. Nature 523 (7561), 425-430
• A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter. ML Oldham, RK Hite, AM Steffen, E Damko, Z Li, T Walz, J Chen. Nature 529 (7587), 537-540
• Atomic structure of the cystic fibrosis transmembrane conductance regulator. Z Zhang, J Chen. Cell 167 (6), 1586-1597. e9
• Structural basis of substrate recognition by the multidrug resistance protein MRP1. ZL Johnson, J Chen. Cell 168 (6), 1075-1085. e9
• Molecular structure of the human CFTR ion channel. F Liu, Z Zhang, L Csanády, DC Gadsby, J Chen. Cell 169 (1), 85-95. e8
• Conformational changes of CFTR upon phosphorylation and ATP binding. Z Zhang, F Liu, J Chen. Cell 170 (3), 483-491. e8
• Molecular structure of human KATP in complex with ATP and ADP. KPK Lee, J Chen, R MacKinnon. Elife 6, e32481
• ATP binding enables substrate release from multidrug resistance protein 1. ZL Johnson, J Chen. Cell 172 (1), 81-89. e10
• Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation. Y Kim, J Chen. Science 359 (6378), 915-919
• Structure of a TRPM2 channel in complex with Ca²⁺ explains unique gating regulation. Z Zhang, B Toth, A Szollosi, J Chen, L Csanady. elife 7, e36409
• Molecular structure of the ATP-bound, phosphorylated human CFTR. Z Zhang, F Liu, J Chen. Proceedings of the National Academy of Sciences 115 (50), 12757-12762
• Structural identification of a hotspot on CFTR for potentiation. F Liu, Z Zhang, A Levit, J Levring, KK Touhara, BK Shoichet, J Chen. Science 364 (6446), 1184-1188

Notes and References

1. Web site: 长沙市一中校友陈珏当选美国国家科学院院士. Yu. Rong. 2019-05-10. Hunan Daily. zh. 2019-05-17.
2. Web site: Alumni News Chen Elected to National Academy of Sciences. 2019-06-06. Ohio University College of Arts & Sciences. en-US. 2020-05-02.
3. Web site: The Rockefeller University » Lab Members. lab.rockefeller.edu. 25 April 2019.
4. Chen. Jue. Lee. Kon Ho. Steinhauer. David A. Stevens. David J. Skehel. John J. Wiley. Don C. October 1998. Structure of the Hemagglutinin Precursor Cleavage Site, a Determinant of Influenza Pathogenicity and the Origin of the Labile Conformation. Cell. 95. 3. 409–417. 10.1016/s0092-8674(00)81771-7. 9814710. 11232474. 0092-8674. free.
5. Chen. J.. Skehel. J. J.. Wiley. D. C.. 1999-08-03. N- and C-terminal residues combine in the fusion-pH influenza hemagglutinin HA2 subunit to form an N cap that terminates the triple-stranded coiled coil. Proceedings of the National Academy of Sciences. 96. 16. 8967–8972. 10.1073/pnas.96.16.8967. 10430879. 17716. 0027-8424. free.
6. Chen. Jue. Skehel. John J.. Wiley. Don C.. September 1998. A Polar Octapeptide Fused to the N-Terminal Fusion Peptide Solubilizes the Influenza Virus HA2Subunit Ectodomain†. Biochemistry. 37. 39. 13643–13649. 10.1021/bi981098l. 9753451. 0006-2960.
7. Chen. Jue. Lu. Gang. Lin. Jeffrey. Davidson. Amy L. Quiocho. Florante A. September 2003. A Tweezers-like Motion of the ATP-Binding Cassette Dimer in an ABC Transport Cycle. Molecular Cell. en. 12. 3. 651–661. 10.1016/j.molcel.2003.08.004. 14527411. free.
8. Web site: Jue Chen, Ph.D.. 2020-07-12. bit.ly.
9. Web site: Jue Chen. 2020-07-12. www.nasonline.org.
10. Web site: Jue Chen . Our Scientists . 25 April 2019 . en.
11. Web site: Jue Chen. 2020-07-12. Our Scientists. en.
12. Web site: 2019 NAS Election. www.nasonline.org. 2020-05-03.
13. Web site: Jue Chen . 2023-10-10 . Our Scientists . en.
14. Web site: Jue Chen . 2023-10-10 . Our Scientists . en.
15. Web site: lori . 2022-04-07 . Chemistry Seminar Alumna, Honorary Degree Recipient Jue Chen, April 29 . 2023-10-10 . Ohio University College of Arts & Sciences . en-US.
16. Web site: 2019 NAS Election. National Academy of Sciences. April 30, 2019.
17. Web site: Jue Chen . 2023-10-10 . scholar.google.com.