Those of us who did a few months of mass spectrometry lectures somewhere in an undergraduate course sometime in the last century, and have had our eyes elsewhere since then, might find that this field is completely unrecognisable. Perhaps, like me, you did some GC-MS of organic compounds extracted from some matrix or used MS as one of the analytical tools to characterise a compound you synthesised. The extension of these ideas to metabolomics-type experiments, and even proteomics is not conceptually challenging (though I admit that the finer points are rather complicated), but the idea that you could use mass spectrometry to get information about the secondary or tertiary structure of a protein or a protein complex might seem far-fetched.

Let me state it boldly: Mass Spectrometry technology has moved on sufficiently that it can be used to look at the secondary and tertiary structures of intact proteins and protein complexes. It happened while I wasn’t looking. It happened a while ago.

An important theme from the  Mass Spectrometry Technologies for Structural Biology conference was the statement of where mass spectrometry fits into structural biology:

– X-ray crystallography provides a very high resolution image, but it is a static snapshot of one possible conformtion

– in NMR the structure seen is an average of the populations present

– the strengths of MS are that it can handle a high level of heterogeneity (and you can tease out many of the different structures) and that you can get dynamic information (on interactions and reactions)

MS spectrum of the yeast eIF3 isolated by tagging subunit eIF3b. Charge state series are assigned on the basis of masses to subcomplexes eIF3i:g, eIF3b:g:i, and eIF3a:b. eIF3i is observed dissociating from the yeast complex at ˜m/z 3,000. (Inset) The interaction network for yeast eIF3 derived from seven subcomplexes observed by MS. Taken from PNAS, 2008.

While Mass Spectrometry is in the title of this conference, and is the common theme throughout all of the experimental work, an important observation from the talks and posters is that the researchers do not use it in isolation. X-ray crystallography, for example, may provide information useful in interpreting the mass spectrometry data or electron microscopy might, for example, provide some information confirming the intermediates suggested by the mass spec results. For the most part, it seems that this is a community that forms strong collaborations.

The speakers were careful to define the instrumental set-up and the potential limitations of their experiments, and there were very lively discussions on these points during the question-times. It is a community that cares deeply about the rigour of their methods.

While I enjoyed the talks, a lot of the detail went over my head. I would therefore very much like to thank some of the PhD students and post-docs who very kindly walked me through their posters, and patiently answered my questions.