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Publications

Recent Publications

Koide, E., Pietz, H. L., Beltran, J., Chen, J. (2024) Structural basis for the transport and regulation mechanism of the Multidrug resistance-associated protein 2. bioRxiv, 2024 Jun 25. doi: 10.1101/2024.06.24.600277

Fiedorczuk, K., Iordanov, I., Mihályi, C., SzöllÅ‘si, A., Csanády, L., and Chen, J. (2024) The structures of protein kinase A in complex with CFTR: mechanisms of phosphorylation and reversible activation. bioRxiv, 2024 Jun 1. doi: 10.1101/2024.05.28.596263

Lee, J., Oldham, M.L., Manon, V., Chen, J. (2024) Principles of peptide selection by the transporter associated with antigen processing. PNAS, 2024 Jun 4;121(23):e2320879121. doi: 10.1073/pnas.2320879121. PMID: 38805290.

Liu, F., Kaplan, A.L., Levring, J., Einsiedel, J., Tiedt, S., Distler, K., Omattage, N.S., Kondratov, I.S., Moroz, Y.S., Pietz, H.L., Irwin, J.J., Gmeiner, P., Shoichet, B.K., Chen, J. (2024) Structure-based discovery of CFTR potentiators and inhibitors. Cell, 2024 Mar 11:2023.09.09.557002. doi: 10.1101/2023.09.09.557002. PMID: 37745391.

Young, P.G., Levring, J., Fiedorczuk, K., Blanchard, S.C., Chen, J. (2024) Structural basis for CFTR inhibition by CFTR(inh)-172. PNAS, 2024 Mar 5;121(10):e2316675121. doi: 10.1073/pnas.2316675121, PMID: 38422021.

Levring, J.,and Chen, J. (2024) Structural identification of a selectivity filter in CFTR. PNAS, 2024 Feb 27;121(9):e2316673121. doi: 10.1073/pnas.2316673121. PMID: 38381791.

Levring, J., Terry, D.S., Kilic, Z. Fitzgerald, G., Blanchard, S., Chen, J. (2023) CFTR function, pathology and pharmacology at single-molecule resolution. Nature, 2023 Apr;616(7957):606-614. doi: 10.1038/s41586-023-05854-7. PMID: 36949202.

Pietz HL, Abbas A, Johnson ZL, Oldham ML, Suga H, Chen J. (2023) A macrocyclic peptide inhibitor traps MRP1 in a catalytically incompetent conformation. PNAS, 2023 Mar 14;120(11):e2220012120. doi: 10.1073/pnas.2220012120. PMID: 36893260.

Fiedorczuk K, Chen J. (2022) Molecular structures reveal synergistic rescue of Δ508 CFTR by Trikafta modulators. Science, 2022 Oct 21;378(6617):284-290. doi: 10.1126/science.ade2216. PMID: 36264792.

Zhao H, Lee J, Chen J. (2022) The hemolysin A secretion system is a multi-engine pump containing three ABC transporters. Cell, 2022 Sep 1;185(18):3329-3340.e13. doi: 10.1016/j.cell.2022.07.017. PMID: 36055198.

Fiedorczuk K, Chen J. (2022) Mechanism of CFTR correction by type I folding correctors. Cell, 2022 Jan 6;185(1):158-168.e11. doi: 10.1016/j.cell.2021.12.009. PMID: 34995514.
Commentary: Science ("In the Pipeline" blog), HHMI News, and Rockefeller Science News

Kieuvongngam V, Chen J. (2022) Structures of the peptidase-containing ABC transporter PCAT1 under equilibrium and nonequilibrium conditions. PNAS, 2022 Jan 5;119 (4) e2120534119. doi: 10.1073/pnas.2120534119. PMID: 35074919.

Liu F, Lee J, Chen J. (2021) Molecular structures of the eukaryotic retinal importer ABCA4. eLife, 2021 Feb 19;10:e63524. doi: 10.7554/eLife.63524. PMID: 33605212.

Kieuvongngam V, Olinares PDB, Palillo A, Oldham ML, Chait BT, Chen J. (2020) Structural basis of substrate recognition by a polypeptide processing and secretion transporter. eLife, 2020 Jan 14;9:e51492 doi: 10.7554/eLife.51492. PMID:31934861.

Wang L, Johnson ZL, Wasserman MR, Levring J, Chen J, Liu S. (2020) Characterization of the kinetic cycle of an ABC transporter by single-molecule and cryo-EM analyses. eLife, 2020 May 27;9:e56451. doi: 10.7554/eLife.56451. PMID: 32458799.

Liu F., Zhang Z., Levit A., Levring J., Touhara K., Shoichet B., Chen J. (2019) Structural identification of a hotspot on CFTR for potentiation. Science, 2019 June 21;364(6446):1184-1188. doi: 10.1126/science.aaw7611.
Commentary in PNAS.

Zhang Z., Liu F., Chen J. (2018) Molecular structure of the ATP-bound, phosphorylated human CFTR. PNAS, 2018 Dec 11;115(50):12757-12762. doi: 10.1073/pnas.1815287115. Epub 2018 Nov 20. PMID: 30459277.

Kim, Y. and Chen, J. (2018) Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformationScience, 25 Jan 2018:eaar7389. doi: 10.1126/science.aar7389. PMID: 29371429.

Lee, K.P.K., Chen, J., and MacKinnon, R. (2017) Molecular structure of human KATP in complex with ATP and ADPeLife, 2017;6:e32481. PMID: 29286281.

Johnson Z.L. and Chen J. (2018) ATP Binding Enables Substrate Release from Multidrug Resistance Protein 1. Cell, 172: 81-89. PMID: 29290467.

Zhang Z., Liu F., and Chen J. (2017) Conformational Changes of CFTR upon Phosphorylation and ATP Binding. Cell, 2017 Jul 27;170(3):483-491.e8. doi: 10.1016/j.cell.2017.06.041. Epub 2017 Jul 20. PMID: 28735752.

Liu F., Zhang Z., Csanády L., Gadsby D.C., Chen J. (2017) Molecular Structure of the Human CFTR Ion Channel. Cell, 2017 Mar 23;169(1):85-95.e8. doi: 10.1016/j.cell.2017.02.024. PMID: 28340353.

Johnson, Z.L., and Chen, J. (2017) Structural basis of substrate recognition by the multidrug resistance protein MRP1. Cell, (168)6: 1075-1085. PMID: 28238471. Covered at Rockefeller NewswireCell, and ACS Chemical Biology

Oldham, M.L., Grigorieff, N., and Chen, J. (2016) Structure of the transporter associated with antigen processing trapped by herpes simplex virus. eLife, 2016 Dec 9;5. PMID: 27935481.

Zhang, Z. and Chen, J. (2016) Atomic structure of the cystic fibrosis transmembrane conductance regulator. Cell, 167(6): 1586-1597. [Full text.] Covered at Rockefeller Newswire and Anatrace.

Oldham, M.L., Hite, R.K., Steffen, A.M., Damko, E., Li, Zi., Walz, T., and Chen, J. (2016) A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter. Nature, 529: 537-540. PMID: 26789246. [Full text]. Covered in Nature Structural and Molecular Biology: News & Views and at Rockefeller Newswire.

Lin, D.Y., Huang, S., and Chen, J. (2015) Crystal structures of a polypeptide processing and secretion transporter. Nature, 523: 425-30. PMID: 26201595 [Pubmed]

Oldham, M.L., Chen, S., and Chen, J. (2013) Structural basis for substrate specificity in the E. coli maltose transport system. PNAS, 110: 18132-18137. [Full text].

Chen, S., Oldham, M.L., Davidson, A.L., and Chen, J. (2013) Carbon catabolite repression of the maltose transporter revealed by X-ray crystallography.  Nature, 499: 364-368. PMID: 23770568. [Pubmed]

Jin, M.S., Oldham, M.L., Zhang, Q., and Chen, J. (2012) Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature, 490: 566-569. PMID: 23000902. [Pubmed]

Lin, D.Y., Diao. J., and Chen, J. (2012) Crystal structures of two bacterial HECT-like E3 ligases in complex with UbcH7 revealing atomic details of pathogen-host interactions.  PNAS, 109, 1925-1930. [Full text].

Oldham, M.L., and Chen, J. (2011) Snapshots of the maltose transporter during ATP hydrolysis. PNAS, 108(37):15152-15156. [Full text]. Comment in PNAS, 108(37): 15015-15016. [Full text].

Oldham, M.L., and Chen, J. (2011) Crystal structure of the maltose transporter in a pre-translocation intermediate state. Science, 332: 1202-1205. [Full text]

Kim, H.C., Steffen, A.M., Oldham, M. L., Chen, J., and Huibregtse, J. M.  (2011) Structure and Function of a HECT Domain Ubiquitin Binding Site. EMBO Reports, 12: 334-341. [Pubmed]

Lin, D.Y., Diao. J., Zhou, D., and Chen, J. (2011) Biochemical and structural studies of a HECT-like ubiquitin ligase from Escherichia coli O157:H7, J. Biol. Chem., 286: 441-449. [Pubmed]

Orelle, C., Alvarez, F. J. D., Oldham, M. L., Orelle, A., Wiley, T. E., Chen, J., and Davidson A. L. (2010) Dynamics of a-helical subdomain rotation in the intact maltose ATP-binding cassette transporter, PNAS, 107(47):20293-20298. [Full text]

Yu, IM, Holdaway, HA, Chipman, PR, Kuhn, RJ, Rossmann, MG, Chen, J (2009) Association of the pr peptides with dengue virus at acidic pH blocks membrane fusion. J Virol. 83(23):12101-12107. [Pubmed]

Khare, D., Oldham, M.L., Orelle, C., Davidson, A.L., and Chen, J (2009) Alternating access in maltose transporter mediated by rigid-body rotations. Mol. Cell,33: 528-536. [Pubmed]

Oldham, M.L., Davidson, A.L., and Chen, J  (2008)  Structural insights into ABC transporter mechanism. Curr Opin Struct Biol., 18(6):726-733. [Pubmed]

Yu, I., Zhang W., Holdaway, H.A., Li,L., Kostyuchenko,V.A., Chipman,P.R., Kuhn,R.J., Rossmann,M.G., and Chen, J. (2008)  Structure of the immature dengue virus at low pH primes proteolytic maturation.  Science, 319:1834-1837. [Pubmed][Full text]

Li, L., Lok, S., Yu, I., Zhang, Y., Kuhn,R.J., Chen, J., and Rossmann,M.G. (2008) The Flavivirus Precursor Membrane-Envelope Protein Complex:  Structure and Maturation.  Science, 319:1830-1834.[Pubmed]

Diao, J., Zhang, Y., Huibregtse, J.M., Zhou,D., and Chen, J. (2008) Crystal structure of SopA, a Salmonella  effector protein mimicking a eukaryotic ubiquitin ligase.  Nat. Struct. & Mol. Biol.,15(1): 65-70. [Pubmed]

Oldham, M.L., Khare, D., Quiocho, Q.A., Davidson, A.L., and Chen, J.  (2007)  Crystal structure of a catalytic intermediate of the maltose transporter.  Nature, 450: 515-521. [Pubmed]

Yu, I., Oldham, M.L., Zhang, J., and Chen, J.  (2006)  Crystal structure of the SARS coronavirus nucleocapsid protein dimerization domain reveals evolutionary linkage between Corona- and Arteri- viridaes. J Biol Chem., 281: 17134-17139. [Pubmed]

Zhang, Y., Higashide, W.M., McCormck, B.A., Chen, J., and Zhou, D. (2006)  The inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase. Mol Microbiol., 62(3): 786-93.[Pubmed]

Lu, G., Westbrooks, J.M., Davidson, A. L., and Chen, J. (2005)  ATP hydrolysis is required to reset the ATP-binding cassette dimer into the resting state conformation. Proc. Natl. Acad. Sci. USA, Dec 13; 102(50):17969-17974. [Pubmed]

Yu, I., Gustafson, C. , Diao, J., Burgner, II J.W., Li, Z., Zhang, J., and Chen, J.  (2005)  Recombinant SARS coronavirus nucleocapsid protein forms a dimer through its C-terminal domain.  J Biol Chem., 280: 23280-86. [Pubmed]

Davidson, A. L. and Chen, J. (2005) Flipping Lipids: Is the third time the charm?  Science, 308:963-965. [Pubmed]

Chang, J., Chen, J., and Zhou, D.  (2005)  Delineation and characterization of the actin nucleation and effector translocation activities of Salmonella SipC. Mol Microbiol. 55(5):1379-89. [Pubmed]

Davidson, A. L. and Chen, J.  (2004)  ATP-binding cassette transporters in bacteria. Annu Rev Biochem. 73:241-268. [Pubmed]

Samanta, S., Ayvaz, T., Reyes, M., Shuman, H.A., Chen, J., and Davidson, A.L.  (2003)  Disulfide crosslinking reveals a site of stable interaction between C-terminal regulatory domains of the two MalK subunits in the maltose transport complex. J Biol Chem., 278:35265-35271. [Pubmed]

Chen, J. Lu, G., Lin, J., Davidson, A. L., and Quiocho, F. A.  (2003)   A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle. Mol. Cell, 12:651-661. [Pubmed]

Earlier Publications

Mao, Y.; J. Chen, J. A. Maynard. B. Zhang, and F. A. Quiocho.  2001.  A novel all helix fold of the AP180 amino terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.  Cell 104:433-440. [Pubmed]

Chen, J., S. Sharma, F. A. Quiocho, and A. L. Davidson.  2001.  Trapping the transition state of an ABC transporter: evidence for a concerted mechanism of maltose transport.  Proc. Natl. Acad. Sci. USA 98:1525-1530. [Pubmed]

Chen, J., S. J. J. Skehel, and D. C. Wiley.  1999.  N- and C-terminal residues combine in the fusion –pH influenza hemmagglutinin HA2 subunit to form an N cap that terminates the triple-stranded coiled coil.  Proc. Natl. Acad. Sci. USA 96:8967-8972. [Pubmed]

Chen, J., J. J. Skehel, and D. C. Wiley.  1998.  A polar octapeptide fused to the N-terminal fusion peptide solubilizes the influenza virus HA2 subunit ectodomain.  Biochemistry 37:13643-13649. [Pubmed]

Chen, J., K. H. Lee, D. A. Steinhauer, D. J. Stevens, J. J. Skehel, and D. C. Wiley.  1998.  Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation.  Cell 95:409-417. [Pubmed]

Chen, J., S. A. Wharton, W. Weissenhorn, L. J. Clader, F. M. Hughson, J. J. Skehel, and D. C. Wiley.  1995.  A soluble domain of the membrane-anchoring chain of influenza virus hemagglutinin (HA2) folds in Escherichia coli into the low-pH-induced conformation.  Proc. Natl. Acad. Sci. USA 92:12205-12209. [Pubmed]

Recent PublicationsKoide, E., Pietz, H. L., Beltran, J., Chen, J. (2024) Structural basis for the transport and regulation mechanism of the Multidrug resistance-associated protein 2. bioRxiv, 2024