All in the family: Structural and evolutionary relationships among three modular proteins with diverse functions and variable assembly

• Published in: Protein science Vol. 7; no. 8; pp. 1661 - 1670
• Main Authors: Bergdoll, Marc, Eltis, Lindsay D., Cameron, Alexander D., Dumas, Philippe, Bolin, Jeffrey T.
• Format: Journal Article
• Language: English
• Published: Bristol Cold Spring Harbor Laboratory Press 01.08.1998
• Subjects: Acetyltransferases; Amino Acid Sequence; Bacterial Proteins - chemistry; bleomycin resistance protein; Burkholderia - chemistry; Crystallography, X-Ray; Dioxygenases; Evolution, Molecular; extradiol dioxygenase; glyoxalase I; Humans; Lactoylglutathione Lyase - chemistry; metalloproteins; Models, Genetic; Models, Molecular; modular proteins; Molecular Sequence Data; Oxygenases - chemistry; Phylogeny; protein evolution; Protein Structure, Secondary; Sequence Homology, Amino Acid; Space life sciences; three‐dimensional domain swapping; extradiol dioxygenase; modular proteins; protein evolution; three-dimensional domain swapping; CRYSTAL-STRUCTURE; PSEUDOMONAS-PUTIDA; bleomycin resistance protein; EXTRADIOL DIOXYGENASES; ESCHERICHIA-COL; glyoxalase I; metalloproteins; NUCLEOTIDE-SEQUENCE
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1002/pro.5560070801

The crystal structures of three proteins of diverse function and low sequence similarity were analyzed to evaluate structural and evolutionary relationships. The proteins include a bacterial bleomycin resistance protein, a bacterial extradiol dioxygenase, and human glyoxalase I. Structural comparisons, as well as phylogenetic analyses, strongly indicate that the modem family of proteins represented by these structures arose through a rich evolutionary history that includes multiple gene duplication and fusion events. These events appear to be historically shared in some cases, but parallel and historically independent in others. A significant early event is proposed to be the establishment of metal‐binding in an oligomeric ancestor prior to the first gene fusion. Variations in the spatial arrangements of homologous modules are observed that are consistent with the structural principles of three‐dimensional domain swapping, but in the unusual context of the formation of larger monomers from smaller dimers or tetramers. The comparisons support a general mechanism for metalloprotein evolution that exploits the symmetry of a homooligomeric protein to originate a metal binding site and relies upon the relaxation of symmetry, as enabled by gene duplication, to establish and refine specific functions.