The recent advancement in moving 'biophysical' analysis of proteins in vivo has finally brought us to a position where we can start to make quantitative comparisons with existing in-vitro data. A striking observation is that protein behaviour in live cells seems, after all, not that different from in test tubes, not even at the level of complex mechanisms like protein aggregation. The example examined in this review is the ALS associated protein SOD1 that apparently retains its in-vitro properties in vivo. Does this mean that the protocols for studying proteins in vivo are somehow oversimplified, or that the macromolecular properties and interplay - despite being intrinsically malleable - are evolutionary more 'streamlined' than previously anticipated? Whatever the answer may be the time is now right to put these data to critical biological test.
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