Insights into kinetochore-DNA interactions from the structure of Cep3Delta.
The CBF3 complex is an essential core component of the budding yeast kinetochore and is required for the centromeric localization of all other kinetochore proteins. We determined the crystal structure of a large section of the protein Cep3 from CBF3, which is the only component with obvious DNA-binding motifs. The protein adopts a roughly bilobal shape, with an extended dimerization interface. The dimer has a large central channel that is sufficient to accommodate duplex B-form DNA. The zinc-finger domains emerge at the edges of the channel, and could bind to the DNA in a pseudo-symmetrical manner at degenerate half-sites in the centromeric sequence. We propose a mechanism for the modulation of DNA affinity by an acidic activator domain, which could be applicable to a wider family of transcription factors.
Macromolecular Structure and Function Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, UK.
Alan
A
Purvis
Martin R
MR
Singleton
D000595:Amino Acid Sequence; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D018386:Kinetochores / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity
C092348:CEP3 protein, S cerevisiae; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA