Mei Hong (chemist)

Mei Hong (born 1970) is a Chinese-American biophysical chemist and Professor of Chemistry at the Massachusetts Institute of Technology.[1] She is known for developing and applying solid-state nuclear magnetic resonance (ssNMR) spectroscopy to understand the structures and mechanisms of membrane proteins, plant cell walls, and amyloid proteins. Hong is a Fellow of the International Society of Magnetic Resonance (ISMAR)[2] and has received the Founders Medal of International Council on Magnetic Resonance in Biological Systems in 2010 and the Günther Laukien Prize in 2014, which is one of the most prestigious awards in the field of Magnetic Resonance research.[3]

Mei Hong

Education and career

Hong grew up in China and completed her bachelor's degree in Chemistry from Mount Holyoke College (summa cum laude) in 1992. She received her Ph.D. degree from the University of California, Berkeley under the direction of Alexander Pines in 1996, where she studied phospholipid structure and dynamics using variable-angle-spinning NMR. After a one-year postdoctoral stint in the laboratory of Robert G. Griffin at the Massachusetts Institute of Technology, she went to University of Massachusetts Amherst and developed biosynthetic isotopic labeling approaches to facilitate protein structure determination by ssNMR. She started an assistant professorship at Iowa State University in 1999, became an associate professor in 2002 and full professor in 2004, and held the first John D. Corbett Professorship from 2007 to 2010. In 2014, she returned to the Massachusetts Institute of Technology as a professor of chemistry.[1]

Research

Hong's research focuses on elucidating the structure, dynamics and mechanism of membrane proteins using ssNMR. She is particularly known for her study of the Matrix-2 (M2) proteins of influenza A viruses, which are responsible for all flu pandemics in history. M2 is an acid-activated proton channel and a membrane scission protein for the influenza virus.[4] Hong's ssNMR studies have provided insights into the proton-conduction mechanism of this channel, by quantifying the proton transfer rates and equilibria between water and the proton-selective histidine residue.[5][6] She showed that the antiviral drug amantadine inhibits proton conduction by direct occlusion of the channel pore.[7] She determined the cholesterol-binding structure of the M2 protein, which sheds light on how cholesterol mediates M2's membrane scission function.[8]

Other membrane proteins that Hong's group has studied include β-hairpin antimicrobial peptides, channel-forming colicins,[9][10] and viral fusion proteins. She determined the structure of the membrane toroidal pores formed by the antimicrobial peptide protegrin-1,[11] which explained the membrane-disruptive mechanism of this peptide. She showed that the transmembrane domain of viral fusion proteins can be structurally plastic, and the β-sheet conformation can correlate with the generation of membrane curvature and membrane dehydration, which are necessary for virus-cell fusion.[12]

Hong has also investigated the structure and dynamics of amyloid proteins, including both neurodegenerative proteins[13] and amyloid fibrils formed by designed peptides.[14] These studies shed light on the origin of structural polymorphism, water interaction,[15] and metal ion binding.

Hong has pioneered the study of plant cell walls using multidimensional ssNMR.[16] These studies revealed the molecular interactions of the polysaccharides in plant cell walls, and helped to revise the conventional model of the primary cell wall structure by proposing a single-network model where cellulose, hemicellulose and pectins all interact with each other.[17] She determined the binding target of the protein expansin to be hemicellulose-enriched regions of cellulose microfibrils,[18] thus giving insight into the mechanism of wall loosening by expansin.  

To address these questions, Hong has developed isotopic labeling strategies,[19] multidimensional NMR correlation experiments,[20] polarization transfer techniques,[21][22] and computational methods for resonance assignment of NMR spectra.[23]

Selected awards and honors

References

  1. "Professor Mei Hong – Hong Lab MIT". Retrieved 2019-05-21.
  2. "The ISMAR Organization | ISMAR". www.weizmann.ac.il. Retrieved 2019-05-21.
  3. Ernst, Richard R. (April 2005). "The Günther Laukien Prize". Journal of Magnetic Resonance. 173 (2): 188–191. Bibcode:2005JMagR.173..188E. doi:10.1016/j.jmr.2005.02.006. ISSN 1090-7807. PMID 15780911.
  4. Hong, Mei; DeGrado, William F. (2012-10-09). "Structural basis for proton conduction and inhibition by the influenza M2 protein". Protein Science. 21 (11): 1620–1633. doi:10.1002/pro.2158. PMC 3527700. PMID 23001990.
  5. Hu, F.; Luo, W.; Hong, M. (2010-10-21). "Mechanisms of Proton Conduction and Gating in Influenza M2 Proton Channels from Solid-State NMR". Science. 330 (6003): 505–508. Bibcode:2010Sci...330..505H. doi:10.1126/science.1191714. ISSN 0036-8075. PMC 4102303. PMID 20966251.
  6. Hu, Fanghao; Schmidt-Rohr, Klaus; Hong, Mei (2011-10-21). "NMR Detection of pH-Dependent Histidine–Water Proton Exchange Reveals the Conduction Mechanism of a Transmembrane Proton Channel". Journal of the American Chemical Society. 134 (8): 3703–3713. doi:10.1021/ja2081185. ISSN 0002-7863. PMC 3288706. PMID 21974716.
  7. Cady, Sarah D.; Schmidt-Rohr, Klaus; Wang, Jun; Soto, Cinque S.; DeGrado, William F.; Hong, Mei (2010). "Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers". Nature. 463 (7281): 689–692. Bibcode:2010Natur.463..689C. doi:10.1038/nature08722. ISSN 0028-0836. PMC 2818718. PMID 20130653.
  8. Elkins, Matthew R.; Williams, Jonathan K.; Gelenter, Martin D.; Dai, Peng; Kwon, Byungsu; Sergeyev, Ivan V.; Pentelute, Bradley L.; Hong, Mei (2017-11-20). "Cholesterol-binding site of the influenza M2 protein in lipid bilayers from solid-state NMR". Proceedings of the National Academy of Sciences. 114 (49): 12946–12951. doi:10.1073/pnas.1715127114. ISSN 0027-8424. PMC 5724280. PMID 29158386.
  9. Hong, Mei; Su, Yongchao (2011-03-07). "Structure and dynamics of cationic membrane peptides and proteins: Insights from solid-state NMR". Protein Science. 20 (4): 641–655. doi:10.1002/pro.600. ISSN 0961-8368. PMC 3081543. PMID 21344534.
  10. Luo, Wenbin; Yao, Xiaolan; Hong, Mei (2005). "Large Structure Rearrangement of Colicin Ia Channel Domain after Membrane Binding from 2D13C Spin Diffusion NMR". Journal of the American Chemical Society. 127 (17): 6402–6408. doi:10.1021/ja0433121. ISSN 0002-7863. PMID 15853348.
  11. Mani, R.; Cady, S. D.; Tang, M.; Waring, A. J.; Lehrer, R. I.; Hong, M. (2006-10-23). "Membrane-dependent oligomeric structure and pore formation of a beta-hairpin antimicrobial peptide in lipid bilayers from solid-state NMR". Proceedings of the National Academy of Sciences. 103 (44): 16242–16247. Bibcode:2006PNAS..10316242M. doi:10.1073/pnas.0605079103. ISSN 0027-8424. PMC 1637567. PMID 17060626.
  12. Yao, Hongwei; Lee, Michelle W.; Waring, Alan J.; Wong, Gerard C. L.; Hong, Mei (2015-08-17). "Viral fusion protein transmembrane domain adopts β-strand structure to facilitate membrane topological changes for virus–cell fusion". Proceedings of the National Academy of Sciences. 112 (35): 10926–10931. Bibcode:2015PNAS..11210926Y. doi:10.1073/pnas.1501430112. ISSN 0027-8424. PMC 4568205. PMID 26283363.
  13. Elkins, Matthew R.; Wang, Tuo; Nick, Mimi; Jo, Hyunil; Lemmin, Thomas; Prusiner, Stanley B.; DeGrado, William F.; Stöhr, Jan; Hong, Mei (2016-07-28). "Structural Polymorphism of Alzheimer's β-Amyloid Fibrils as Controlled by an E22 Switch: A Solid-State NMR Study". Journal of the American Chemical Society. 138 (31): 9840–9852. doi:10.1021/jacs.6b03715. hdl:1721.1/113318. ISSN 0002-7863. PMC 5149419. PMID 27414264.
  14. Lee, M.; Wang, T.; Makhlynets, O.V.; Wu, Y.; Polizzi, N.; Wu, H.; Gosavi, P.M.; Korendovych, I.V.; DeGrado, W.F. (2017-05-31). "Zinc-Binding Structure of a Catalytic Amyloid from Solid-State NMR Spectroscopy". doi:10.2210/pdb5ugk/pdb. Cite journal requires |journal= (help)
  15. Wang, Tuo; Jo, Hyunil; DeGrado, William F.; Hong, Mei (2017-04-21). "Water Distribution, Dynamics, and Interactions with Alzheimer's β-Amyloid Fibrils Investigated by Solid-State NMR". Journal of the American Chemical Society. 139 (17): 6242–6252. doi:10.1021/jacs.7b02089. ISSN 0002-7863. PMC 5808936. PMID 28406028.
  16. Wang, Tuo; Hong, Mei (2015-09-09). "Solid-state NMR investigations of cellulose structure and interactions with matrix polysaccharides in plant primary cell walls". Journal of Experimental Botany. 67 (2): 503–514. doi:10.1093/jxb/erv416. ISSN 0022-0957. PMC 6280985. PMID 26355148.
  17. Dick-Pérez, Marilú; Zhang, Yuan; Hayes, Jennifer; Salazar, Andre; Zabotina, Olga A.; Hong, Mei (2011-02-15). "Structure and Interactions of Plant Cell-Wall Polysaccharides by Two- and Three-Dimensional Magic-Angle-Spinning Solid-State NMR". Biochemistry. 50 (6): 989–1000. doi:10.1021/bi101795q. ISSN 0006-2960. PMID 21204530.
  18. Wang, T.; Park, Y. B.; Caporini, M. A.; Rosay, M.; Zhong, L.; Cosgrove, D. J.; Hong, M. (2013-09-24). "Sensitivity-enhanced solid-state NMR detection of expansin's target in plant cell walls". Proceedings of the National Academy of Sciences. 110 (41): 16444–16449. Bibcode:2013PNAS..11016444W. doi:10.1073/pnas.1316290110. ISSN 0027-8424. PMC 3799313. PMID 24065828.
  19. Hong, Mei (1999). "Determination of Multiple φ-Torsion Angles in Proteins by Selective and Extensive 13C Labeling and Two-Dimensional Solid-State NMR". Journal of Magnetic Resonance. 139 (2): 389–401. Bibcode:1999JMagR.139..389H. doi:10.1006/jmre.1999.1805. ISSN 1090-7807. PMID 10423377.
  20. deAzevedo, E.R.; Kennedy, S.B.; Hong, M. (2000). "Determination of slow motions in extensively isotopically labeled proteins by magic-angle-spinning 13C-detected 15N exchange NMR". Chemical Physics Letters. 321 (1–2): 43–48. Bibcode:2000CPL...321...43D. doi:10.1016/s0009-2614(00)00310-9. ISSN 0009-2614.
  21. Hong, Mei; Schmidt-Rohr, Klaus (2013-02-07). "Magic-Angle-Spinning NMR Techniques for Measuring Long-Range Distances in Biological Macromolecules". Accounts of Chemical Research. 46 (9): 2154–2163. doi:10.1021/ar300294x. ISSN 0001-4842. PMC 3714308. PMID 23387532.
  22. Roos, Matthias; Mandala, Venkata S.; Hong, Mei (2018-09-13). "Determination of Long-Range Distances by Fast Magic-Angle-Spinning Radiofrequency-Driven 19F–19F Dipolar Recoupling NMR". The Journal of Physical Chemistry B. 122 (40): 9302–9313. doi:10.1021/acs.jpcb.8b06878. ISSN 1520-6106. PMC 6314681. PMID 30211552.
  23. Fritzsching, K. J.; Yang, Y.; Schmidt-Rohr, K.; Hong, Mei (2013-04-28). "Practical use of chemical shift databases for protein solid-state NMR: 2D chemical shift maps and amino-acid assignment with secondary-structure information". Journal of Biomolecular NMR. 56 (2): 155–167. doi:10.1007/s10858-013-9732-z. ISSN 0925-2738. PMC 4048757. PMID 23625364.
  24. "Monday at ENC: Laukien Prize Winners 2014". The Resonance. 2014-03-25. Retrieved 2019-05-21.
  25. "ICMRBS Founders Medal". www.icmrbs.org. Retrieved 2019-05-21.
  26. "Elected Fellows". American Association for the Advancement of Science. Retrieved 2019-05-21.
  27. "ACS Award in Pure Chemistry". American Chemical Society. Retrieved 2019-05-21.
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