Ann Taylor/sandbox Norovirus oligosaccaride binding

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Binding of the Norovirus to fucose containing oligosaccarides


Norovirus causes deadly diarrhea. Understanding how it works will allow us to design prevention.

The outside of the Norovirus is made up of a protein cover. It binds to carbohydrates found on cells, enters the cell, takes over the transcription machinery to make lots of copies of the viral RNA, then ruptures the cell, spilling out new copies of the norovirus...while at the same time, triggering vomiting and diarrhea. It is very infectious and there is no specific medicine that can shorten the infection time...yet.

A recent paper [1] described that oligosaccharides from human breast milk can preferentially bind to the viral capsid, preventing binding to the digestive system cells and giving some protection from infection.

The structures in this page are from this paper [2]

Look at the cartoon view of the virus protein. Is it predominantly alpha helical, beta sheet, or a mixture?

How many peptide chains make up the quaternary structure?

Look at this view of the carbohydrate (shown in spacefill) interacting with amino acids in the protein (shown as ball and stick). What kind of intermolecular forces help the carbohydrate bind to the protein?



norovirus capsid binding to oligosaccarides

Drag the structure with the mouse to rotate

References

  1. Hanisch FG, Hansman GS, Morozov V, Kunz C, Schroten H. Avidity of alpha-fucose on human milk oligosaccharides and blood group-unrelated oligo/polyfucoses is essential for potent norovirus-binding targets. J Biol Chem. 2018 Jul 27;293(30):11955-11965. doi: 10.1074/jbc.RA117.001369. Epub, 2018 Jun 1. PMID:29858242 doi:http://dx.doi.org/10.1074/jbc.RA117.001369
  2. Cao S, Lou Z, Tan M, Chen Y, Liu Y, Zhang Z, Zhang XC, Jiang X, Li X, Rao Z. Structural basis for the recognition of blood group trisaccharides by norovirus. J Virol. 2007 Jun;81(11):5949-57. Epub 2007 Mar 28. PMID:17392366 doi:10.1128/JVI.00219-07

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Ann Taylor

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