Fig. 6: The proposed folding threshold model of protein evolution.
From: Secretory quality control constrains functional selection-associated protein structure innovation
Functional constraints play a major role in shaping protein evolution, yet a folding threshold imposed by the eukaryotic quality control must be satisfied first before functional selection can be effective for a large portion of secretory and luminal proteins. Therefore, mutations that disrupt the original fold without giving rise to an alternative stable fold are equivalent to functional knockout. Only those that meet the threshold will be selected further leading to functional improvement and/or adaptation.
