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Proteins as Play‐Doh: Evolution May Utilize Local Structural Plasticity to Alter Protein Folds
Author(s) -
Szyszka Taylor,
Kumirov Vlad,
Cordes Matthew
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.882.5
Subject(s) - plasticity , microbiology and biotechnology , chemistry , computational biology , biology , materials science , composite material
Protein fold evolution is a process by which protein structure is altered over time creating the mosaic of diverse protein folds that exists today. A model system for studying protein fold evolution consists of two members of the Cro protein family that have 40% sequence identity but different structures, one all α‐helical (Xfaso1) and the other mixed α‐helix and β‐sheet (Pfl6). Previous work showed that hybrids of these two sequences have combinations of α and β conformations unlike either parent sequence, suggesting that new folds could evolve from preexisting folds in several steps. One such hybrid, XPH1, has the sequence of Xfaso1 with 9 mutations from Pfl6, and has a structure less helical than Xfaso1, but more helical than Pfl6. Here, we introduced subsets of the 9 mutations into Xfaso1 and analyzed the resulting mutant proteins via circular dichroism and NMR to determine which of the 9 mutations were necessary to change the structure of Xfaso1 to that of XPH1. We found that only the E40G and V48Y mutations together were necessary to change the all‐α structure of Xfaso1 to that of XPH1. The structural plasticity of helical Cro proteins implies that α‐helical folds could have evolved into α+β folds through multiple structural intermediates.