Resolving Extended N-Glycans by NMR: New Insights into Influenza Hemagglutinin N-Glycan Interactions

Session: 
PS1 Poster session 1 Odd numbers
Code: 
P57
Location (hall): 
Foyer
Start/end time: 
Monday, July 1, 2019 - 15:45 to 17:15
Beatriz
Fernández de Toro Ronda

Beatriz Fernández de Toro Ronda1, Wenjie Peng2,3, Andrew Thompson3, Gema Domínguez4, F. Javier Cañada1,5, Javier Pérez Castells4, James C. Paulson3, Jesús Jiménez Barbero6,7, Ángeles Canales8

1Dpto Biología Estructural y Química, Centro de Investigaciones Biológicas CSIC, Madrid, Spain, 2Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China, 3Depts. of Mol Med and Immunol and Microbiol, The Scripps Research Institute, San Diego, USA, 4Dpto Química, Fac. Farmacia, Universidad San Pablo CEU, Madrid, Spain, 5CIBER of Respiratory Diseases (CIBERES), , Spain, 6CIC bioGUNE, Bizkaia Science and Technology Park, Bilbao, Spain, 7IKERBASQUE, Basque Foundation for Science, Bilbao, Spain, 8Dpto Química Orgánica I, Fac. Ciencias Químicas, Universidad Complutense de Madrid, Madrid, Spain

Seasonal flu (influenza virus infection) is one of the major threats to human health, causing of up to 500 thousand deaths worldwide annually).[1,2] Hemagglutinin, a glycoprotein presented in the surface of the influenza virus, binds sialylated N-glycans located on the surface of host epithelial cells.

The structural elucidation and the conformational studies of N-glycans remain a challenge due to the complexity, heterogeneity and flexibility of carbohydrates. Moreover, the isochronous chemical shifts presented for the same units located at different branches make impossible the distinction of their signals in the NMR spectra.

Taking advantage of the lanthanide approach, an unambiguous assignment of each carbohydrate unit has been reached for bianntenary N-glycans containing one and two LacNAc units, permitting their conformational elucidation and the recognition study of these N-glycans by the HK/68 hemagglutinin strain.[3]

Left: Structure of the N-glycan containing 2 LacNAc units. Right: Extension of the H4 galactoses region of the ¹H-¹³C HSQC spectrum.

References: 
  1. Influenza (Flu) | CDC https://www.cdc.gov/flu/ (accessed May 8, 2019).
  2. Petrova, V. N.; Russell, C. A. Nat. Rev. Microbiol. 2017, 16 (1), 47–60.
  3. Fernández de Toro, B.; Peng, W.; Thompson, A. J.; Domínguez, G.; Cañada, F. J.; Pérez-Castells, J.; Paulson, J. C.; Jiménez-Barbero, J.; Canales, Á. Angew. Chemie Int. Ed. 2018, 57 (46), 15051–15055.

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