Structural Similarity between Histone Chaperone Cia1p/Asf1p and DNA-Binding Protein NF-[kappa]B

The structural relationships between histone-binding proteins and DNA-binding proteins are important, since nucleosome-interacting factors possess histone-binding and/or DNA-binding components. S. cerevisiae (Sc) Cia1p/Asf1p, a homologue of human CIA (CCG1-interacting factor A), is the most evolutionarily conserved histone chaperone, which facilitates nucleosome assembly by interacting with the nucleosome entry site of the core histones H3/H4. The crystal structure of the evolutionarily conserved domain (residues 1-169) of Cia1p (ScCia1p-[Delta]C2) was determined at 2.95 Å resolution. The refined model contains 166 residues in the asymmetric unit. The overall tertiary structure resembles a {szligbeta}-sandwich fold, and belongs to the "switched" immunoglobulin class of proteins. The crystal structure suggests that ScCia1p-[Delta]C2 is structurally related to the DNA-binding proteins, such as NF-[kappa]B and its family members. This is the first examination of the structural similarities between a histone chaperone and DNA-binding proteins. We discuss the possibilities that the strands {szligbeta}3 and {szligbeta}4, which possess highly electronegative surface potentials, are the important regions for the interaction with core histones, and that the histone chaperone ScCia1p/Asf1p and the DNA-binding protein NF-[kappa]B may have evolved from the same prototypal protein class.