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Protein complexes take flight

Nature Structural Biology volume 9, pages 505–506 (2002)Cite this article

The origins of the electrospray process can be traced back to the 19th century when it was used for spray coating of surfaces. Today its use as an ionization method is regarded as one of the most significant breakthroughs in mass spectrometry. However, its widespread acceptance as an ionization technique has been relatively slow. Up until the late 1980s the ultimate goal for ionization methods had been to create singly charged ions and molecular fragments from which chemical structure could be deduced. Consequently the coupling of electrospray with mass spectrometry was initially derided since it produces multiply charged ions with little or no fragmentation1. For this reason it was not until the late 1980s that the first mass spectra of proteins were reported2. With this breakthrough came the rapid realization of its potential. Its most enticing aspects were that, unlike its predecessors, electrospray did not require high vacuum or heat to deliver gaseous ions. Instead, pressure was applied to deliver an appropriate flow of liquid through a needle maintained at kilovolt potential. Simply by moving along a large electric field gradient the emerging liquid droplet became charged. This charge was subsequently transferred to proteins during desolvation to produce naked gas phase ions and the mass-to-charge spectrum recorded in a quadrupole mass spectrometer. For the first time in its history, mass spectrometry could deliver protein ions formed directly from their solution state by a remarkably simple process.

Electrospray mass spectrometry rapidly became established as a method that enabled very precise measurement of molecular weights of proteins3. Because the most efficient electrospray was carried out in high proportions of acidified organic solvent at elevated temperatures, this had two important consequences for proteins. First, for an average protein, typically 10–60 positive or negative charges would be acquired depending on the polarity of the voltage. Consequently the mass-to-charge ratio of proteins was generally below 3,000, the upper limit for detection of most quadrupole mass spectrometers. The second consequence of these solvent conditions was that the mass spectra that were recorded corresponded to proteins that were highly charged and denatured. The native state of the protein was destroyed while in solution, prior to the electrospray process. A major challenge during the 1990s was therefore to try to overcome this denaturation step. Below is a personal view of these developments.

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  1. Professor of Mass Spectrometry in the University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK

    Carol V. Robinson

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Robinson, C. Protein complexes take flight. Nat Struct Mol Biol 9, 505–506 (2002). https://doi.org/10.1038/nsb0702-505

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