Structural similarity between histone chaperone Cia1p/Asf1p and DNA-binding protein NF-kappaB.
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-DeltaC2) was determined at 2.95 A resolution. The refined model contains 166 residues in the asymmetric unit. The overall tertiary structure resembles a beta-sandwich fold, and belongs to the "switched" immunoglobulin class of proteins. The crystal structure suggests that ScCia1p-DeltaC2 is structurally related to the DNA-binding proteins, such as NF-kappaB 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 beta3 and beta4, 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-kappaB may have evolved from the same prototypal protein class.
Padmanabhan
Balasundaram
B
Horikoshi Gene Selector Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST), 5-9-6 Tokodai, Tsukuba 300-2635.
Kataoka
Kazuhiro
K
Umehara
Takashi
T
Adachi
Naruhiko
N
Yokoyama
Shigeyuki
S
Horikoshi
Masami
M
D018797:Cell Cycle Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006657:Histones; D018832:Molecular Chaperones / Q000737:chemistry*; D016328:NF-kappa B / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D040681:Structural Homology, Protein
C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; C472823:Cia1p protein, S cerevisiae; D006657:Histones; D018832:Molecular Chaperones; D016328:NF-kappa B; D029701:Saccharomyces cerevisiae Proteins