title: Multiple co-evolutionary networks are supported by the common tertiary scaffold of the LacI/GalR proteins.
abstract: Protein families might evolve paralogous functions on their common tertiary scaffold in two ways. First, the locations of functionally-important sites might be "hard-wired" into the structure, with novel functions evolved by altering the amino acid (e.g. Ala vs Ser) at these positions. Alternatively, the tertiary scaffold might be adaptable, accommodating a unique set of functionally important sites for each paralogous function. To discriminate between these possibilities, we compared the set of functionally important sites in the six largest paralogous subfamilies of the LacI/GalR transcription repressor family. LacI/GalR paralogs share a common tertiary structure, but have low sequence identity (≤ 30%), and regulate a variety of metabolic processes. Functionally important positions were identified by conservation and co-evolutionary sequence analyses. Results showed that conserved positions use a mixture of the "hard-wired" and "accommodating" scaffold frameworks, but that the co-evolution networks were highly dissimilar between any pair of subfamilies. Therefore, the tertiary structure can accommodate multiple networks of functionally important positions. This possibility should be included when designing and interpreting sequence analyses of other protein families. Software implementing conservation and co-evolution analyses is available at https://sourceforge.net/projects/coevolutils/.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Parente
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Liskin
authors.initials: L
authors.lastname: Swint-Kruse
mesh_terms: D001483:Base Sequence; D020134:Catalytic Domain / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D056968:Lac Repressors / Q000737:chemistry / Q000235:genetics*; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010802:Phylogeny; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D012984:Software
chemical_list: D029968:Escherichia coli Proteins; C050993:Galactose repressor proteins; D056968:Lac Repressors; D012097:Repressor Proteins