X-ray structural analysis of the yeast cell cycle regulator Swi6 reveals variations of the ankyrin fold and has implications for Swi6 function.
Swi6 is a 92,000 Mr protein common to two distinct transcriptional activation complexes (SBF and MBF) that coordinate gene expression at the G1-S boundary of the yeast cell cycle. The X-ray structure of a central 36,000 Mr fragment has been determined and refined at 2.1 A resolution. The structure reveals a basic framework of five ankyrin repeat modules that is elaborated through a series of helical insertions distinguishing it from structures of other ankyrin repeat proteins. A second domain contains an approximately 30-residue region of extended structure that interacts with the ankyrin repeat core over a substantial proportion of its surface. Conservation of residues buried by these interactions indicates that all members of the Swi6/Cdc10 family share a similar architecture. Several temperature-sensitive mutations within Swi6 and Cdc10 appear to disrupt these interdomain contacts rather than destabilize the ankyrin repeat core. The unusual domain arrangement may be crucial for the modulation of interactions with other co-regulatory molecules such as cyclin-CDK complexes, and has implications for the quaternary interactions within the multisubunit SBF and MBF transcription complexes.
Division of Protein Structure, National Institute for Medical Research, London, UK.
R
R
Foord
I A
IA
Taylor
S G
SG
Sedgwick
S J
SJ
Smerdon
D000595:Amino Acid Sequence; D017487:Ankyrins / Q000737:chemistry*; D018797:Cell Cycle Proteins / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry*; D014961:X-Ray Diffraction
D017487:Ankyrins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C075111:SWI6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors