Sunday, March 17, 2024

Asparagine to iso-aspartage conversion in norovirus infection!


Holy cow, y'all, this one was definitely not a fun puzzle for these authors to sort out! 

The punchline here is that there is a spontaneous post-translational modification - get this one - it is a deamidation of asparagine - which makes it the exact same mass as aspartate - that changes both the protein 3D structure AND alters binding partners.

How do you go about even suggesting that is what is happening? It seems like they started with trying to model the norovirus capsid protein by NMR and it was fuzzy and suggested two forms. They ended up doing a lot of NMR and hydrogen deuterium exchange mass spectrometry. 

Deamidations are very easy to mistake for naturally occurring isotopes, so they used inline automated pepsin digestion and used 120,000 resolution on the MS/MS spectra (!!!) to help properly resolve the fragments and this story. Seriously, just a monumental effort to show how a tiny and extremely simple virus can use clever biochemistry (I've never heard of at all until now!) to cause complex things to happen. 

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