It’s a pleasure to welcome Guy Lippens to this group. We feature his latest paper on the in-cell NMR analysis of the human protein tau (implicated in Alzheimer’s disease). For details see his 2008 paper. I encourage everyone interested in in-cell NMR spectroscopy to read it. The paper contains amazing quality in-cell NMR spectra of a protein that is intrinsically unfolded over the entire length of its protein sequence (~400aa) and hence has very good signal to noise. In addition, Guy and his coworkers demonstrate the feasibility of in-cell NMR measurements at intracellular concentrations of 5uM(!) tau and report the observation of different phosphorylation states of this protein.

If you know about the biology of tau, i.e. that it binds to microtubules (components of the cytoskeleton i.e. very big) when not phoshporylated, it is very surprising that one can actually see tau in Xenopus laevis oocytes (solution state NMR after all and size matters)! Bare in mind that microtubules are amongst the most abundant proteins in the cell and at 5uM tau we are clearly in the physiological (and stochiometric) range.

I myself have always told people who asked me whether I tried tau that I was not thinking it was going to work because of its biology.

Beats the odds!