Origins of globular structure in proteins

Abstract
Since natural proteins are the products of a long evolutionary process, the structural properties of present‐day proteins should depend not only on physico‐chemical constraints, but also on evolutionary constraints. Here we propose a model for protein evolution, in which membranes play a key role as a scaffold for supporting the gradual evolution from flexible polypeptides to well‐folded proteins. We suggest that the folding process of present‐day globular proteins is a relic of this putative evolutionary process. To test the hypothesis that membranes once acted as a cradle for the folding of globular proteins, extensive research on membrane proteins and the interactions of globular proteins with membranes will be required.

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