Most of us who teach protein structure have very likely stood in front of a class at some point and confidently stated that any two naturally occurring proteins displaying 40% sequence identity will be homologous and thus possess the same fold. A paper by Roessler et al. (1) in a recent issue of PNAS has definitively overturned this basic tenet by demonstrating that a pair of protein homologues displaying 40% identity exhibit markedly different folds. These proteins are both repressors of the Cro family and were identified in prophage sequences present in the genomes of the bacterial species, Pseudomonas fluorescens (Pfl 6) and Xy-lella fastidiosa (Xfaso 1). The atomic resolution structures of these proteins, solved by Roessler et al.
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