Abstract
Twenty-five years ago, we obtained our first mass spectra of molecular chaperones in complex with protein ligands and entered a new field of gas-phase structural biology. It is perhaps now time to pause and reflect, and to ask how many of our initial structure predictions and models derived from mass spectrometry (MS) datasets were correct. With recent advances in structure determination, many of the most challenging complexes that we studied over the years have become tractable by other structural biology approaches enabling such comparisons to be made. Moreover, in the light of powerful new electron microscopy methods, what role is there now for MS? In considering these questions, I will give my personal view on progress and problems as well as my predictions for future directions.
Highlights
In the early days of applying mass spectrometry (MS) to structural biology, our development of methods to study the folding of proteins was viewed with much cautious scepticism
Much remained to be explored about the extent of folded structure that survives the phase change and the time scales involved in transfer into the gas phase, but for me this was evidence that at least some aspects of protein secondary structure could be preserved
It was during these protein-folding experiments that I first noticed that the appearance of folded protein coincided with the time point at which binding of the cofactor took place
Summary
From molecular chaperones to membrane motors: through the lens of a mass spectrometrist. Twenty-five years ago, we obtained our first mass spectra of molecular chaperones in complex with protein ligands and entered a new field of gas-phase structural biology. It is perhaps time to pause and reflect, and to ask how many of our initial structure predictions and models derived from mass spectrometry (MS) datasets were correct. With recent advances in structure determination, many of the most challenging complexes that we studied over the years have become tractable by other structural biology approaches enabling such comparisons to be made. In the light of powerful new electron microscopy methods, what role is there for MS? I will give my personal view on progress and problems as well as my predictions for future directions In the light of powerful new electron microscopy methods, what role is there for MS? In considering these questions, I will give my personal view on progress and problems as well as my predictions for future directions
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