TY - JOUR
T1 - Extreme divergence between one-to-one orthologs
T2 - The structure of N15 Cro bound to operator DNA and its relationship to the λ Cro complex
AU - Hall, Branwen M.
AU - Roberts, Sue A.
AU - Cordes, Matthew H.J.
N1 - Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2019/7/26
Y1 - 2019/7/26
N2 - The gene cro promotes lytic growth of phages through binding of Cro protein dimers to regulatory DNA sites. Most Cro proteins are one-to-one orthologs, yet their sequence, structure and binding site sequences are quite divergent across lambdoid phages. We report the cocrystal structure of bacteriophage N15 Cro with a symmetric consensus site. We contrast this complex with an orthologous structure from phage λ, which has a dissimilar binding site sequence and a Cro protein that is highly divergent in sequence, dimerization interface and protein fold. The N15 Cro complex has less DNA bending and smaller DNA-induced changes in protein structure. N15 Cro makes fewer direct contacts and hydrogen bonds to bases, relying mostly on water-mediated and Van der Waals contacts to recognize the sequence. The recognition helices of N15 Cro and λ Cro make mostly nonhomologous and nonanalogous contacts. Interface alignment scores show that half-site binding geometries of N15 Cro and λ Cro are less similar to each other than to distantly related CI repressors. Despite this divergence, the Cro family shows several code-like protein-DNA sequence covariations. In some cases, orthologous genes can achieve a similar biological function using very different specific molecular interactions.
AB - The gene cro promotes lytic growth of phages through binding of Cro protein dimers to regulatory DNA sites. Most Cro proteins are one-to-one orthologs, yet their sequence, structure and binding site sequences are quite divergent across lambdoid phages. We report the cocrystal structure of bacteriophage N15 Cro with a symmetric consensus site. We contrast this complex with an orthologous structure from phage λ, which has a dissimilar binding site sequence and a Cro protein that is highly divergent in sequence, dimerization interface and protein fold. The N15 Cro complex has less DNA bending and smaller DNA-induced changes in protein structure. N15 Cro makes fewer direct contacts and hydrogen bonds to bases, relying mostly on water-mediated and Van der Waals contacts to recognize the sequence. The recognition helices of N15 Cro and λ Cro make mostly nonhomologous and nonanalogous contacts. Interface alignment scores show that half-site binding geometries of N15 Cro and λ Cro are less similar to each other than to distantly related CI repressors. Despite this divergence, the Cro family shows several code-like protein-DNA sequence covariations. In some cases, orthologous genes can achieve a similar biological function using very different specific molecular interactions.
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U2 - 10.1093/nar/gkz507
DO - 10.1093/nar/gkz507
M3 - Article
C2 - 31180482
AN - SCOPUS:85070185024
SN - 0305-1048
VL - 47
SP - 7118
EP - 7129
JO - Nucleic acids research
JF - Nucleic acids research
IS - 13
ER -