Credit: © 2009 ACS

Many cellular processes involve intricate molecular machines built from assemblies of proteins. Understanding how these machines work requires the ability to watch in real time the structural changes that occur in these assemblies as they perform their biological function. Nuclear magnetic resonance (NMR) spectroscopy experiments are attractive because of the atomic resolution capabilities. However, the ability to follow the action in real time requires a short relaxation time — the time taken to return to an equilibrium distribution of spins after a pulse — so that subsequent pulses can be delivered quickly.

Now, Jérôme Boisbouvier and co-workers from the Institut de Biologie Structurale in Grenoble and ETH Zürich have shown1 that the time resolution of 2D-NMR experiments can be reduced to less than a second. Their technique — called SOFAST-methyl-TROSY — relies on measuring NMR signals for specific protonated methyl groups in an otherwise deuterated protein. Two different methyl groups — one on an alanine residue and one on an isoleucine residue (close to and distant from the polypeptide backbone) — are used as structural probes.

This allowed the delay between subsequent scans to be reduced to a few milliseconds, and enabled the researchers to record high quality proton–carbon correlation spectra for a complex protein in just a few seconds.