Biophysics Journal Club

Evidence for the principle of minimal frustration in the evolution of protein folding landscapes

Wed, 09 Aug 2017 1:00 PM
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Biophysics Journal Club
Evidence for the principle of minimal frustration in the evolution of protein folding landscapes

Emma Lathouwers
Department of Physics, SFU

Aug 9, 2017 at 1:00pm in P8445.2

Synopsis

Franco O Tzul, Daniel Vasilchuk, and George I Makhatadze
PNAS 114, E1627-E1632 – Published 14 February 2017

Theoretical and experimental studies have firmly established that protein folding can be described by a funneled energy landscape. This funneled energy landscape is the result of foldable protein sequences evolving following the principle of minimal frustration, which allows proteins to rapidly fold to their native biologically functional conformations. For a protein family with a given functional fold, the principle of minimal frustration suggests that, independent of sequence, all proteins within this family should fold with similar rates. However, depending on the optimal living temperature of the organism, proteins also need to modulate their thermodynamic stability. Consequently, the difference in thermodynamic stability should be primarily caused by differences in the unfolding rates. To test this hypothesis experimentally, we performed comprehensive thermodynamic and kinetic analyses of 15 different proteins from the thioredoxin family. Eight of these thioredoxins were extant proteins from psychrophilic, mesophilic, or thermophilic organisms. The other seven protein sequences were obtained using ancestral sequence reconstruction and can be dated back over 4 billion years. We found that all studied proteins fold with very similar rates but unfold with rates that differ up to three orders of magnitude. The unfolding rates correlate well with the thermodynamic stability of the proteins. Moreover, proteins that unfold slower are more resistant to proteolysis. These results provide direct experimental support to the principle of minimal frustration hypothesis.